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Sample records for 1-year open-label study

  1. Risperidone in Children with Disruptive Behavior Disorders and Subaverage Intelligence: A 1-Year, Open-Label Study of 504 Patients

    ERIC Educational Resources Information Center

    Croonenberghs, Jan; Fegert, Joerg M.; Findling, Robert L.; de Smedt, Goedele; van Dongen, Stefan

    2005-01-01

    Objective: To determine the long-term safety and effectiveness of risperidone for severe disruptive behaviors in children. Method: A multisite, 1-year, open-label study of patients aged 5 to 14 years with disruptive behaviors and subaverage intelligence was conducted. Results: Seventy-three percent of the 504 patients enrolled completed the study.…

  2. An Analysis of Patient Adherence to Treatment during a 1-Year, Open-Label Study of OROS[R] Methylphenidate in Children with ADHD

    ERIC Educational Resources Information Center

    Faraone, Stephen V.; Biederman, Joseph; Zimmerman, Brenda

    2007-01-01

    Objective: Treatment adherence is an important aspect of ADHD symptom management, but there are many factors that may influence adherence. Method: This analysis assessed adherence to OROS methylphenidate during a 1-year, open-label study in children. Adherence was defined as the number of days medication was taken divided by the number of days in…

  3. Effect of a low-dose contraceptive patch on efficacy, bleeding pattern, and safety: a 1-year, multicenter, open-label, uncontrolled study.

    PubMed

    Wiegratz, Inka; Bassol, Susana; Weisberg, Edith; Mellinger, Uwe; Merz, Martin

    2014-12-01

    This Phase III, uncontrolled, open-label, multicenter study was conducted to investigate the contraceptive efficacy, bleeding pattern, and cycle control of a novel once-a-week contraceptive patch, delivering low-dose ethinyl estradiol (EE) and gestodene (GSD) at the same systemic exposure seen after oral administration of a combined oral contraceptive containing 0.02 mg EE/0.06 mg GSD. Participants were women aged 18 to 35 years, all of whom received the EE/GSD patch for 13 cycles each of 21 treatment days (one patch per week for 3 weeks) followed by a 7-day, patch-free interval. The primary efficacy variable was the occurrence of unintended pregnancies during the study period as assessed by life table analysis and the Pearl Index. Secondary efficacy variables were days with bleeding during four 90-day reference periods and during 1 treatment year, bleeding pattern, and cycle control. The Kaplan-Meier probability of contraceptive protection after 364 treatment days was 98.8% and the adjusted Pearl Index was 0.81. The percentage of participants with intracyclic bleeding/spotting decreased over time, from 11.4% to 6.8% in cycles 1 and 12, respectively. Almost all participants (range: 90.8%-97.6%) experienced withdrawal bleeding across the study period. Compliance was very high (mean: 97.9%; median: 100%). The most frequent adverse events were headache (9.5%) and application site reaction (8.5%); no clinically significant safety concerns were observed. Results suggest the EE/GSD patch is highly effective in preventing pregnancy. Menstrual bleeding pattern was favorable and within the ranges expected of a healthy female population. The patch was well tolerated and treatment compliance was high.

  4. Effect of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes: A 1-year, open-label randomized study

    PubMed Central

    Kuchay, Mohammad Shafi; Laway, Bashir Ahmad; Bashir, Mir Iftikhar; Wani, Arshad Iqbal; Misgar, Raiz Ahmad; Shah, Zaffar Amin

    2015-01-01

    Background: Whether Vitamin D supplementation in prediabetes subjects prevents the development of diabetes is a matter of debate, and the results are inconsistent. This open-label, randomized study in subjects with prediabetes evaluated the effect of 12 months of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes in an ethnically homogeneous Kashmiri population. Materials and Methods: A total of 147 subjects were diagnosed as prediabetes out of which 137 subjects were randomized to receive in addition to standard lifestyle measures, either Vitamin D 60,000 IU weekly for 4 weeks and then 60,000 IU monthly (n = 69) or no Vitamin D (n = 68). Fasting plasma glucose (FPG), 2-h plasma glucose and A1C levels were estimated at 0, 6 and 12 months. Changes in FPG, 2-h plasma glucose, A1C level and the proportion of subjects developing diabetes were assessed among 129 subjects. Results: At 12 months, A1C levels were significantly lesser (5.7% ± 0.4%) in the Vitamin D supplemented group when compared with non-Vitamin D supplemented (6.0% ± 0.3%). Similarly, FPG (97 ± 7) and 2-h plasma glucose (132 ± 16) were significantly less in Vitamin D supplemented group as compared with non-Vitamin D supplemented group (FPG = 116 ± 6 and 2-h plasma glucose = 157 ± 25) at 12 months. Nine out of 65 in non-Vitamin D supplemented and seven out of 64 in the Vitamin D supplemented group developed diabetes. Conclusions: Vitamin D supplementation in prediabetes subjects significantly lowered FPG, 2-h plasma glucose and A1C levels. PMID:25932396

  5. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study.

    PubMed

    Moore, Angela; Kempers, Steven; Murakawa, George; Weiss, Jonathan; Tauscher, Amanda; Swinyer, Leonard; Liu, Hong; Leoni, Matthew

    2014-01-01

    Once-daily topical brimonidine tartrate (BT) gel 0.5% was shown to be efficacious and safe for the treatment of erythema of rosacea in previous studies including a 4-week treatment phase. In the present 1-year study, we aimed to assess the long-term safety and efficacy of the treatment. Subjects with moderate to severe erythema of rosacea were instructed to apply topical BT gel 0.5% once daily for 12 months. Severity of erythema and adverse events (AEs) were evaluated. Approximately 345 subject years of exposure to BT gel 0.5% was achieved in the study. The incidence of AEs and AEs judged to be related to the study drug was higher at the beginning and decreased over the course of the study. Similar safety profiles were observed between the subjects who had received or not received concomitant therapies for the inflammatory lesions of rosacea. Effect of topical BT gel 0.5% on erythema severity was observed after the first application and the durability of the effect was maintained until the end of the study at month 12, with no tachyphylaxis observed. In conclusion, once-daily topical BT gel 0.5% is safe and consistently effective for the long-term treatment of moderate to severe erythema of rosacea, even in the presence of concomitant therapies for the inflammatory lesions of rosacea.

  6. Tocotrienol Treatment in Familial Dysautonomia: Open-Label Pilot Study.

    PubMed

    Cheishvili, David; Maayan, Channa; Holzer, Naama; Tsenter, Jeanna; Lax, Elad; Petropoulos, Sophie; Razin, Aharon

    2016-07-01

    Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy, primarily presented in Ashkenazi Jews. The most common mutation in FD patients results from a single base pair substitution of an intronic splice site in the IKBKAP gene which disrupts normal mRNA splicing and leads to tissue-specific reduction of IKBKAP protein (IKAP). To date, treatment of FD patients remains preventative, symptomatic and supportive. Based on previous in vitro evidence that tocotrienols, members of the vitamin E family, upregulate transcription of the IKBKAP gene, we aimed to investigate whether a similar effects was observed in vivo. In the current study, we assessed the effects of tocotrienol treatment on FD patients' symptoms and IKBKAP expression in white blood cells. The initial daily doses of 50 or 100 mg tocotrienol, doubled after 3 months, was administered to 32 FD patients. Twenty-eight FD patients completed the 6-month study. The first 3 months of tocotrienol treatment was associated with a significant increase in IKBKAP expression level in FD patients' blood. Despite doubling the dose after the initial 3 months of treatment, IKBKAP expression level returned to baseline by the end of the 6-month treatment. Clinical improvement was noted in the reported clinical questionnaire (with regard to dizziness, bloching, sweating, number of pneumonia, cough episodes, and walking stability), however, no significant effect was observed in any clinical measurements (weight, height, oxygen saturation, blood pressure, tear production, histamine test, vibration threshold test, nerve conduction, and heart rate variability) following Tocotrienol treatment. In conclusion, tocotrienol treatment appears significantly beneficial by clinical evaluation for some FD patients in a few clinical parameters; however it was not significant by clinical measurements. This open-label study shows the complexity of effect of tocotrienol treatment on FD patients' clinical outcomes and on

  7. Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial

    PubMed Central

    Spiera, Robert F; Gordon, Jessica K; Mersten, Jamie N; Magro, Cynthia M; Mehta, Mansi; Wildman, Horatio F; Kloiber, Stacey; Kirou, Kyriakos A; Lyman, Stephen; Crow, Mary K

    2011-01-01

    Objective To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc). Methods In this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were treated with imatinib 400 mg daily. Patients were monitored monthly for safety assessments. Modified Rodnan skin scores (MRSS) were assessed every 3 months. Pulmonary function testing, chest radiography, echocardiography and skin biopsies were performed at baseline and after 12 months of treatment. Results Twenty-four patients completed 12 months of therapy. 171 adverse events (AE) with possible relation to imatinib were identified; 97.6% were grade 1 or 2. Twenty-four serious AE were identified, two of which were attributed to study medication. MRSS decreased by 6.6 points or 22.4% at 12 months (p=0.001). This change was evident starting at the 6-month time point (Δ=−4.5; p<0.001) and was seen in patients with both early and late-stage disease. Forced vital capacity (FVC) improved by 6.4% predicted (p=0.008), and the diffusion capacity remained stable. The improvement in FVC was significantly greater in patients without interstitial lung disease. Health-related quality of life measures improved or remained stable. Blinded dermatopathological analysis confirmed a significant decrease in skin thickness and improvement in skin morphology. Conclusions Treatment with imatinib was tolerated by most patients in this cohort. Although AE were common, most were mild to moderate. In this open-label experience, improvements in skin thickening and FVC were observed. Further investigation of tyrosine kinase inhibition for dcSSc in a double-blind randomised placebo controlled trial is warranted. ClinicalTrials.gov, NCT00555581 PMID:21398330

  8. Levetiracetam in autistic children: an open-label study.

    PubMed

    Rugino, Thomas A; Samsock, Teresa C

    2002-08-01

    The objectives of this study were to determine whether autistic children taking levetiracetam (1) showed improvement in the areas of aggression, impulsivity, hyperkinesis, and mood instability, and (2) showed a nootropic response. Ten white autistic boys ranging from 4 to 10 years were compared pretreatment and while taking levetiracetam for an average of 4.1 weeks. Inattention, hyperkinesis, and impulsivity were evaluated using the Achenbach Attention Problems scale, Conners DSM-IV Total scale, and the Conners Attention-Deficit Hyperactivity Disorder Index scale, all of which showed statistically significant improvements. Mood instability was measured with the Conners Global Index (CGI) Emotional Lability and CGI Total scales, both of which showed statistically significant improvements. Aggressive behavior, as measured with the Achenbach Aggression scale, showed statistically significant improvement only for subjects who were not recently weaned from medications that reduce aggression (e.g., risperidone, carbamazepine, desipramine). Levetiracetam may reduce hyperactivity, impulsivity, mood instability, and aggression in autistic children with these problems. No nootropic effect was observed.

  9. An open-label naturalistic pilot study of acamprosate in youth with autistic disorder.

    PubMed

    Erickson, Craig A; Early, Maureen; Stigler, Kimberly A; Wink, Logan K; Mullett, Jennifer E; McDougle, Christopher J

    2011-12-01

    To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration-approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects.

  10. ADHD Treatment with Once-Daily OROS Methylphenidate: Final Results from a Long-term Open-Label Study

    ERIC Educational Resources Information Center

    Wilens, Timothy; McBurnett, Keith; Stein, Mark; Lerner, Marc; Spencer, Thomas; Wolraich, Mark

    2005-01-01

    Objective: Few studies have assessed effectiveness and tolerability of stimulants when used for prolonged periods in children with attention-deficit/hyperactivity disorder (ADHD). This article presents final results from an open-label, multisite study of a once-daily formulation of methylphenidate (MPH), OROS[R] MPH. Method: Subjects received OROS…

  11. Long-term intrathecal ziconotide for chronic pain: an open-label study.

    PubMed

    Webster, Lynn R; Fisher, Robert; Charapata, Steven; Wallace, Mark S

    2009-03-01

    This open-label multicenter study evaluated the long-term safety and efficacy of intrathecal ziconotide and included 78 patients with chronic pain who had completed one of two previous ziconotide clinical trials. Each patient's initial ziconotide dose was based on his or her dose from the study of origin and was adjusted as necessary on the basis of adverse events and analgesic effect. The median ziconotide dose was 6.48 mcg/day (range, 0.00-120.00 mcg/day) at the Initial Visit and ranged from 5.52 to 7.20 mcg/day across all study visits. The most commonly reported new adverse events that were considered ziconotide related were memory impairment (11.3%); dizziness, nystagmus, and speech disorder (8.5% each); nervousness and somnolence (7.0% each); and abnormal gait (5.6%). There was no evidence of increased adverse event incidence at higher cumulative ziconotide doses. Elevations in creatine kinase were noted, but the proportion of patients with creatine kinase elevations did not change from the Initial Visit to the Termination Visit (4.1% each). Stable mean Visual Analog Scale of Pain Intensity scores during the three years of the study suggested no evidence of increased pain intensity with increased duration of ziconotide exposure. Long-term treatment with ziconotide appeared to be well tolerated and effective in patients whose response to ziconotide and ability to tolerate the drug had been previously demonstrated. PMID:18715748

  12. Rotigotine Objectively Improves Sleep in Parkinson's Disease: An Open-Label Pilot Study with Actigraphic Recording.

    PubMed

    Calandra-Buonaura, Giovanna; Guaraldi, Pietro; Doria, Andrea; Zanigni, Stefano; Nassetti, Stefania; Favoni, Valentina; Cevoli, Sabina; Provini, Federica; Cortelli, Pietro

    2016-01-01

    Sleep disturbances represent important predictors of poor quality of life (QoL) in Parkinson's disease (PD). This open-label pilot study aimed to objectively assess, by means of actigraphic recording, effect of rotigotine on sleep in PD patients with self-reported sleep complaints. 15 PD patients underwent one-week actigraphic recording before (T0) and during (T1) rotigotine treatment, which was titrated to the dose subjectively improving motor symptoms (4-8 mg/24 h). Sleep disturbances, daytime sleepiness, cognitive performance, QoL, and depression were also evaluated with questionnaires. Actigraphic recordings showed a significant reduction in nocturnal motor activity and mean duration of wake episodes after sleep onset during rotigotine treatment compared to baseline. In 10 patients presenting objective evidence of poor sleep quality at T0 (sleep efficiency ≤ 85%), rotigotine also significantly improved other sleep parameters and further reduced nocturnal motor activity and mean duration of wake episodes. A significant decrease in number and duration of daytime sleep episodes was also observed at T1. Finally we confirmed that rotigotine significantly improves perceived sleep quality and QoL. Our study showed for the first time that rotigotine is associated with an objective improvement of nocturnal and diurnal sleep disturbances in PD patients with self-reported sleep complaints. This study is registered with AIFA-observational study registry number 12021.

  13. Rotigotine Objectively Improves Sleep in Parkinson's Disease: An Open-Label Pilot Study with Actigraphic Recording

    PubMed Central

    Calandra-Buonaura, Giovanna; Guaraldi, Pietro; Doria, Andrea; Zanigni, Stefano; Nassetti, Stefania; Favoni, Valentina; Cevoli, Sabina; Provini, Federica; Cortelli, Pietro

    2016-01-01

    Sleep disturbances represent important predictors of poor quality of life (QoL) in Parkinson's disease (PD). This open-label pilot study aimed to objectively assess, by means of actigraphic recording, effect of rotigotine on sleep in PD patients with self-reported sleep complaints. 15 PD patients underwent one-week actigraphic recording before (T0) and during (T1) rotigotine treatment, which was titrated to the dose subjectively improving motor symptoms (4–8 mg/24 h). Sleep disturbances, daytime sleepiness, cognitive performance, QoL, and depression were also evaluated with questionnaires. Actigraphic recordings showed a significant reduction in nocturnal motor activity and mean duration of wake episodes after sleep onset during rotigotine treatment compared to baseline. In 10 patients presenting objective evidence of poor sleep quality at T0 (sleep efficiency ≤ 85%), rotigotine also significantly improved other sleep parameters and further reduced nocturnal motor activity and mean duration of wake episodes. A significant decrease in number and duration of daytime sleep episodes was also observed at T1. Finally we confirmed that rotigotine significantly improves perceived sleep quality and QoL. Our study showed for the first time that rotigotine is associated with an objective improvement of nocturnal and diurnal sleep disturbances in PD patients with self-reported sleep complaints. This study is registered with AIFA-observational study registry number 12021. PMID:26981312

  14. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD

    PubMed Central

    Khindri, Sanjeev; Vahdati-Bolouri, Mitra; Church, Alison; Fahy, William A.

    2016-01-01

    This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0–24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score). Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: −50 mL) to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: −5–54). Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37%) and glycopyrronium (36%). Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments. PMID:27730198

  15. Efficacy and tolerability of quetiapine in cluster B personality disorder: an open-label study.

    PubMed

    Le Bloc'h, Yves; Baumann, Pierre; Stigler, Michael; Eap, Chin B; Zullino, Daniele F; Le Bloc'h, Yves; Baumann, Pierre; Stigler, Michael; Eap, Chin B; Zullino, Daniele F

    2007-01-01

    Objective. The aim of this open-label 8-week study was to assess the effectiveness of quetiapine on aggressive behaviour and social dysfunctions in patients suffering from a cluster B personality disorder (DSM-IV). Methods. The visits were performed at baseline and at days 14, 28 and 56. After a standard titration schedule, the patients received a dose augmented or reduced dose, within a range from 50 to 400 mg/day during the visits, depending on efficacy and tolerance. Assessment of efficacy was based on the French version of the Social Disability and Aggression Scale SDAS (SDAS-21). Response was defined as a decrease of ≥50% reduction of the total scores compared to baseline. Tolerability was assessed with the CGI, UKU, EPS-scales. Results and conclusion. Eight of the 12 patients included received 200 mg/day quetiapine after titration (all patients: 50-400 mg/day). At week 8, five out of 12 patients were responders based on the SDAS-21 scores for the average expression of the symptoms, and six out of 12 on the basis of SDAS-21 scores for the peak expression. There was a significant correlation between weight change and total SDAS variation (Kendall's τb= -0.644; p=0.02). These findings should be reexamined in further studies.

  16. Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Proof of Concept Study

    PubMed Central

    Sharma, Alok; Gokulchandran, Nandini; Sane, Hemangi; Nagrajan, Anjana; Kulkarni, Pooja; Shetty, Akshata; Mishra, Priti; Kali, Mrudula; Biju, Hema; Badhe, Prerna

    2013-01-01

    Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs) intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7). Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT) scan recorded objective changes. Out of 32 patients, a total of 29 (91%) patients improved on total ISAA scores and 20 patients (62%) showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P < 0.001) on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism. PMID:24062774

  17. An open-label study of naftifine hydrochloride 1% gel in the treatment of tinea versicolor.

    PubMed

    Gold, Michael H; Bridges, Tancy; Avakian, Edward; Plaum, Stefan; Pappert, Eric J; Fleischer, Alan B; Hardas, Bhushan

    2011-01-01

    Tinea versicolor (TV) is a superficial cutaneous fungal infection characterized by cutaneous pigment changes, pruritus, scaling, and erythema. This open-label, single-center pilot study evaluated the efficacy and safety of naftifine 1% gel applied twice daily for 2 weeks in 10 men and women (median age 38 years) with TV. Baseline mycology status was determined by potassium hydroxide (KOH) and microscopy and clinical symptom severity (CSS) scored by the investigator using a 0 to 9 scale (0=absent, 9=worst). Patients applied naftifine HCI 1% gel to the affected area twice daily for 14 days. They returned for follow-up efficacy and safety assessments at the end of treatment (week 2), 2 weeks after treatment (week 4), and 6 weeks after treatment (week 8). All patients had a positive mycology at baseline; one was KOH negative at week 2, two were negative at week 4, and five (50%) were negative at week 8. Mean investigator total CSS score decreased from a baseline value of 4.7 to 3.2 at week 2 (32% improvement), 2.6 at week 4 (45% improvement), and 2.7 at week 8 (43% improvement). The patients rated their symptoms to be improved at all follow-up visits. There were no treatment-related adverse events during the study. These results suggest that naftifine 1% gel is a safe and efficacious topical treatment for TV. PMID:22165042

  18. Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

    PubMed Central

    Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

    2016-01-01

    Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

  19. STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

    ERIC Educational Resources Information Center

    Erickson, Craig A.; Veenstra-Vanderweele, Jeremy M.; Melmed, Raun D.; McCracken, James T.; Ginsberg, Lawrence D.; Sikich, Linmarie; Scahill, Lawrence; Cherubini, Maryann; Zarevics, Peter; Walton-Bowen, Karen; Carpenter, Randall L.; Bear, Mark F.; Wang, Paul P.; King, Bryan H.

    2014-01-01

    STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32…

  20. An open label, prospective, clinical study on a polyherbal formulation in osteoarthritis of knee

    PubMed Central

    Nipanikar, Sanjay U.; Saluja, Manjit; Kuber, Vinod V.; Kadbhane, Kalyan P.; Chopra, Arvind; Khade, Namdev R.

    2013-01-01

    Background: Currently, though pharmacological, mechanical, and surgical interventions are used, there is no known cure for osteoarthritis (OA). Objectives: The main aim of the study was to assess the efficacy and safety of “TLPL/AY/03/2008”, a polyherbal formulation on knee joint pain assessed on visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Materials and Methods: It was an open label, single center, prospective, clinical study conducted in 36 patients of OA Knee. Two capsules of ‘TLPL/AY/03/2008’ were given to all patients twice daily orally after meals for 180 days. Results: Data describing quantitative measures are expressed as mean ± SD. Comparison of variables representing categorical data was performed using Chi-square test. The mean joint pain (as assessed on VAS) reduced significantly (59.85%; P < 0.05) and the mean WOMAC combined score, WOMAC pain sub-score, WOMAC stiffness sub-score, and WOMAC difficulty sub-score also reduced significantly at the end of the study. The mean time taken by the patients to walk 50 feet too, was reduced significantly (25.26%) at the end of the study. At the end of 4 months of the treatment, no patient needed paracetamol as rescue medicine to control pain. Most of the patients had shown good overall improvement assessed by the physician and by the patients. Majority of the patients showed excellent tolerability to the study drug. No significant change in most of the safety laboratory parameters was observed at the end of the study. Conclusion: The study provides good evidence in support of the efficacy and safety of the ‘TLPL/AY/03/2008’ in OA of knee. PMID:23741160

  1. Three open-label studies of oral interferon alpha in the treatment of HIV disease.

    PubMed

    Jordan, W C

    1994-04-01

    Three open-label studies were conducted in which natural human interferon-alpha (nHuIFN-alpha) was given orally to human immunodeficiency virus (HIV)-infected patients at a daily dosage of 150 IU for 12 months in an attempt to assess the effects of this treatment on their CD4+ cell counts. In the first study, 110 patients received nHuIFN-alpha, and 142 patients received nHuIFN-alpha and azidothymidine (AZT). At 12 months, patients given nHuIFN-alpha alone had a mean increase of 14% in their CD4+ counts, although the mean increase in absolute CD4+ count was similar between the groups. Blacks in this study were more likely to experience an increase in CD4+ count than other ethnic groups (P < 0.001). In the second study, 40 black, male homosexuals with CD4+ count between 350 and 500/mm3 were enrolled in groups of 10 to receive either nHuIFN-alpha or AZT, or both nHuIFN-alpha and AZT, or nothing (untreated controls). At 12 months, the mean CD4+ counts of the patients in the group given nHuIFN-alpha alone were significantly higher than the mean CD4+ counts in both the group given AZT alone and the untreated controls (P < 0.01). In the third study, 38 patients with CD4+ cell counts > 700/mm3 were enrolled in groups of 19, matched by gender and ethnic group, to receive nHuIFN-alpha or nothing (untreated controls). Patients given nHuIFN-alpha experienced a mean increase of 12% in their CD4+ counts by the end of the 12-month study.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease

    PubMed Central

    Sibley, Cailin H; Chioato, Andrea; Felix, Sandra; Colin, Laurence; Chakraborty, Abhijit; Plass, Nikki; Rodriguez-Smith, Jackeline; Brewer, Carmen; King, Kelly; Zalewski, Christopher; Kim, H Jeffrey; Bishop, Rachel; Abrams, Ken; Stone, Deborah; Chapelle, Dawn; Kost, Bahar; Snyder, Christopher; Butman, John A; Wesley, Robert; Goldbach-Mansky, Raphaela

    2014-01-01

    Objective To study efficacy and safety of escalating doses of canakinumab, a fully human anti-IL-1β monoclonal antibody in the severe cryopyrin-associated periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID). Methods 6 patients were enrolled in this 24-month, open-label phase I/II study. All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was 150 mg (or 2 mg/kg in patients ≤40 kg) or 300 mg (or 4 mg/kg) with escalation up to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patientreported clinical components and measures of systemic inflammation and CNS inflammation. Hearing, vision and safety were assessed. Primary endpoint was full remission at month 6. Results All patients flared after anakinra withdrawal, and symptoms and serum inflammatory markers improved with canakinumab. All patients required dose escalation to the maximum dose. At month 6, none had full remission, although 4/6 achieved inflammatory remission, based on disease activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6 due to persistent CNS leucocytosis. At the last study visit, 5/6 patients achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual acuity and field were stable in all patients, progressive hearing loss occurred in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a methicillin-resistant Staphylococcus aureus infection) occurred. Conclusions Canakinumab at the studied doses improves symptoms and serum inflammatory features of NOMID, although low-grade CNS leukocytosis in four patients and headaches in one additional patient persisted. Whether further dose intensifications are beneficial in these cases remains to be assessed. ClinicalTrials.gov identifier NCT00770601. PMID:24906637

  3. An Open Label Pilot Study of Adjunctive Asenapine for the Treatment of Posttraumatic Stress Disorder

    PubMed Central

    Pilkinton, Patricia; Berry, Carlos; Norrholm, Seth; Bartolucci, Al; Birur, Badari; Davis, Lori L.

    2016-01-01

    Objective Selective serotonin reuptake inhibitors (SSRIs) remain the first-line treatment for posttraumatic stress disorder (PTSD). However, adjunctive atypical antipsychotics are often used to target residual or refractory symptoms. Asenapine is a novel atypical antipsychotic that possesses a high serotonin (5-HT2A) to dopamine (D2) affinity ratio and alpha-adrenergic antagonism, which may be advantageous in treating PTSD. This pilot study aimed to identify the therapeutic potential of asenapine as an adjunctive treatment for PTSD. Method Eighteen subjects initiated treatment in this single-site prospective, open-label, 12-week trial of flexibly-dosed asenapine in Veterans with PTSD who had not responded to an adequate course of treatment with an SSRI, venlafaxine, or mirtazapine. Subjects remained on their antidepressant medication and were started on adjunctive asenapine 5 mg sublingual at bedtime, which was gradually titrated to a maximum of 10 mg twice per day, as tolerated. The primary outcome measure was the Clinician Administered PTSD Scale (CAPS) for DSM-IV. Results Fifteen subjects finished at least 4 weeks and eleven completed the 12 week study. There was a significant and clinically meaningful decrease in CAPS from baseline (77.56 ± 14.48) to week 4 (48.7 ± 30.6), and to week 12 (35.3 ± 19.7). Six participants experienced adverse events possibly related to asenapine; however, only three participants discontinued early due to related adverse events. Conclusion This pilot study demonstrated that adjunctive treatment with asenapine may provide additional benefit to some patients experiencing residual PTSD symptoms in spite of optimal antidepressant therapy. A larger efficacy study may be warranted. PMID:27738377

  4. Safety of long-term use of linezolid: results of an open-label study

    PubMed Central

    Vazquez, Jose A; Arnold, Anthony C; Swanson, Robert N; Biswas, Pinaki; Bassetti, Matteo

    2016-01-01

    Objective The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. Results The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50–254 days). In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs) included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk, and central scotomas in each eye. Conclusion In our small population, linezolid was generally well tolerated and AEs were consistent with the known safety profile. Extensive ophthalmologic testing of all 24 linezolid-treated patients identified one case adjudicated as probable, linezolid-associated optic neuropathy. PMID:27621644

  5. Safety of long-term use of linezolid: results of an open-label study

    PubMed Central

    Vazquez, Jose A; Arnold, Anthony C; Swanson, Robert N; Biswas, Pinaki; Bassetti, Matteo

    2016-01-01

    Objective The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. Results The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50–254 days). In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs) included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk, and central scotomas in each eye. Conclusion In our small population, linezolid was generally well tolerated and AEs were consistent with the known safety profile. Extensive ophthalmologic testing of all 24 linezolid-treated patients identified one case adjudicated as probable, linezolid-associated optic neuropathy.

  6. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam.

    PubMed

    Yates, Stephen L; Fakhoury, Toufic; Liang, Wei; Eckhardt, Klaus; Borghs, Simon; D'Souza, Joseph

    2015-11-01

    We evaluated nonpsychotic behavioral adverse events (BAEs) in patients receiving levetiracetam (LEV) who switched to brivaracetam (BRV). Patients ≥16 years of age, receiving 2-3 antiepileptic drugs (AEDs), including LEV 1-3g/day, and experiencing BAEs within 16 weeks of LEV treatment initiation, enrolled in an open-label Phase 3b study (NCT01653262) comprising a ≤1-week screening period, an immediate switch from LEV to BRV 200mg/day (without titration), and a 12-week treatment period. The percentages of patients with investigator-assessed clinically meaningful reduction in BAEs, shift in maximum BAE intensity, and change in health-related quality of life (HRQoL) (Patient-Weighted Quality of Life in Epilepsy Inventory-Form 31 [QOLIE-31-P]) were assessed. Of 29 patients enrolled, 26 (89.7%) completed the study. At the end of the treatment period, 27/29 (93.1%) patients switched to BRV had clinically meaningful reductions in BAEs. Physicians reported a reduction in the maximum intensity of primary BAEs in 27/29 (93.1%) patients. Mean change from baseline to Week 12 in QOLIE-31-P total score was 12.1, indicating improved HRQoL. During the treatment period, 23/29 (79.3%) patients reported treatment-emergent adverse events (TEAEs). One patient reported a serious TEAE (suicidal ideation and suicide attempt). Two patients discontinued BRV because of TEAEs. Findings from this small study suggest that patients experiencing BAEs associated with LEV may benefit from switching to BRV.

  7. The Efficacy of Neurofeedback in Patients with Major Depressive Disorder: An Open Labeled Prospective Study.

    PubMed

    Cheon, Eun-Jin; Koo, Bon-Hoon; Choi, Joong-Hyun

    2016-03-01

    The purpose of this study was to evaluate the effect of neurofeedback on depressive symptoms and electrophysiological disturbances in patients with major depressive disorder. We recruited participants suffering from depression to evaluate efficacy of left prefrontal beta with alpha/theta training. An 8-week, prospective, open-label study was undertaken. Twenty participants were recruited. The treatment protocol was twice or three times a week training of beta at F3 with alpha/theta at Pz for 8 weeks. When every visit, patients were received beta training for 30 min, and then alpha/theta training for 30 min. Baseline, 4 and 8 week scores of; the Hamilton rating scale for Depression (HAM-D), the Hamilton rating scale for Anxiety (HAM-A), the Beck Depression Inventory (BDI)-II, the Beck Anxiety Inventory (BAI), Clinical global impression-severity (CGI-S), and pre- and post-treatment resting state EEGs were compared. Interhemispheric alpha power asymmetry (A score) was computed for homologous sites F3-F4. Pre- and post-training clinical assessments revealed significant improvements in HAM-D, HAM-A, BDI, and CGI-S scores. Cumulative response rates by HAM-D were 35.0 and 75.0 % at 4 and 8 weeks, respectively, corresponding cumulative remission rates by HAM-D were 15.0 and 55.0 %, respectively. No significant differences were found between pre- and post-treatment A score. Neurofeedback treatment could improve depressive symptoms significantly. In addition, anxiety symptoms and clinical illness severity decreased significantly after neurofeedback treatment. Despite its several limitations, such as, small sample size and lack of a control group, this study suggested neurofeedback has significant effects in patients with major depressive disorder. PMID:26392114

  8. Synthetic ACTH in High Risk Patients with Idiopathic Membranous Nephropathy: A Prospective, Open Label Cohort Study

    PubMed Central

    van de Logt, Anne-Els; Beerenhout, Charles H.; Brink, Hans S.; van de Kerkhof, Jos J.; Wetzels, Jack F.; Hofstra, Julia M.

    2015-01-01

    New therapeutic agents are warranted in idiopathic membranous nephropathy. Synthetic ACTH may be advantageous with reported remission rates up to 85% and few side effects. We conducted a prospective open label cohort study from 2008 till 2010 (NCT00694863). We prospectively selected patients with idiopathic membranous nephropathy and high risk for progression (defined as βeta-2-microglobulin (β2m) excretion of >500 ng/min). For comparison, we selected matched historical controls treated with cyclophosphamide. The prospectively selected patients received intramuscular injections of synthetic ACTH during 9 months (maximal dose 1 mg twice a week). The primary endpoints concerned the feasibility and incidence of remissions as a primary event. Secondary endpoints included side effects of treatment and the incidence of remissions and relapses at long-term follow-up. Twenty patients (15 men) were included (age 54±14 years, serum creatinine 104 μmol/l [IQR 90–113], urine protein:creatinine ratio 8.7 g/10 mmol creatinine [IQR 4.3–11.1]). Seventeen patients (85%) completed treatment. 97% of injections were administered correctly. Cumulative remission rate was 55% (complete remission in 4 patients, partial remission 7 patients). In a group of historical controls treated with cyclophosphamide and steroids, 19 of 20 patients (95%) developed a remission (complete remission in 13 patients, partial remission in 6 patients) (p<0.01). The main limitation of our study is its small size and the use of a historical control group. We show that treatment with intramuscular injections of synthetic ACTH is feasible. Our data suggest that synthetic ACTH is less effective than cyclophosphamide in inducing a remission in high risk patients with idiopathic membranous nephropathy. The use of synthetic ACTH was also associated with many adverse events. Therefore, we advise against synthetic ACTH as standard treatment in membranous nephropathy. Trial Registration ClinicalTrials.gov NCT

  9. Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Fung, Lawrence K.; Libove, Robin A.; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y.

    2014-01-01

    The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse…

  10. An open-label study of memantine treatment in 3 subtypes of frontotemporal lobar degeneration.

    PubMed

    Boxer, Adam L; Lipton, Anne M; Womack, Kyle; Merrilees, Jennifer; Neuhaus, John; Pavlic, Danijela; Gandhi, Anisha; Red, Dana; Martin-Cook, Kristen; Svetlik, Doris; Miller, Bruce L

    2009-01-01

    There are currently no Food and Drug Administration-approved treatments for frontotemporal lobar degeneration (FTLD). The objectives of this study were to explore the tolerability of memantine treatment in FTLD and to monitor for possible effects on behavior, cognition, and function. Forty-three individuals who met clinical criteria for FTLD [21 with frontotemporal dementia (FTD), 13 with semantic dementia (SD), and 9 with progressive nonfluent aphasia (PA)] received 26 weeks of open-label treatment with memantine at a target dose of 20 mg daily. Concurrent treatment with acetylcholinesterase inhibitors was prohibited. Cognitive and functional outcome measures included the Mini Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog), clinical dementia rating-sum of boxes, Neuropsychiatric Inventory (NPI), Frontal Behavior Inventory, Executive Interview (EXIT25), Texas Functional Living Scale (TFLS), Geriatric Depression Scale, and Unified Parkinson's Disease Rating Scale-motor scale. Most subjects were able to tolerate the target dose of memantine. A transient improvement was observed on the total NPI score primarily in the FTD group. Variable declines were observed on the ADAS-cog, EXIT25, Frontal Behavior Inventory, NPI, TFLS, and UPDRS scores. The FTD and SD groups declined on most of the cognitive and behavioral outcome measures, but remained stable on the UPDRS, whereas the progressive nonfluent aphasia group remained relatively stable on the ADAS-cog, NPI, and TFLS, but declined on the UPDRS. Memantine was well-tolerated in these subjects. Future placebo-controlled trials of memantine in FTLD are warranted and may have greater power to detect behavioral and cognitive effects if focused on the FTD and SD clinical syndromes. PMID:19812461

  11. Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study

    PubMed Central

    Fornaro, Michele; McCarthy, Michael J; De Berardis, Domenico; De Pasquale, Concetta; Tabaton, Massimo; Martino, Matteo; Colicchio, Salvatore; Cattaneo, Carlo Ignazio; D’Angelo, Emanuela; Fornaro, Pantaleo

    2013-01-01

    Purpose The circadian rhythm hypothesis of bipolar disorder (BD) suggests a role for melatonin in regulating mood, thus extending the interest toward the melatonergic antidepressant agomelatine as well as type I (acute) or II cases of bipolar depression. Patients and methods Twenty-eight depressed BD-II patients received open label agomelatine (25 mg/bedtime) for 6 consecutive weeks as an adjunct to treatment with lithium or valproate, followed by an optional treatment extension of 30 weeks. Measures included the Hamilton depression scale, Pittsburgh Sleep Quality Index, the Clinical Global Impression Scale–Bipolar Version, Young Mania Rating Scale, and body mass index. Results Intent to treat analysis results demonstrated that 18 of the 28 subjects (64%) showed medication response after 6 weeks (primary study endpoint), while 24 of the 28 subjects (86%) responded by 36 weeks. When examining primary mood stabilizer treatment, 12 of the 17 (70.6%) valproate and six of the 11 (54.5%) lithium patients responded by the first endpoint. At 36 weeks, 14 valproate treated (82.4%) and 10 lithium treated (90.9%) subjects responded. At 36 weeks, there was a slight yet statistically significant (P = 0.001) reduction in body mass index and Pittsburgh Sleep Quality Index scores compared to respective baseline values, regardless of mood stabilizer/outcome. Treatment related drop-out cases included four patients (14.28%) at week 6 two valproate-treated subjects with pseudo-vertigo and drug-induced hypomania, respectively, and two lithium-treated subjects with insomnia and mania, respectively. Week 36 drop outs were two hypomanic cases, one per group. Conclusion Agomelatine 25 mg/day was an effective and well-tolerated adjunct to valproate/lithium for acute depression in BD-II, suggesting the need for confirmation by future double blind, controlled clinical trials. PMID:23430979

  12. Efficacy and safety of escitalopram versus desvenlafaxine in the treatment of major depression: A preliminary 1-year prospective randomized open label comparative trial

    PubMed Central

    Gupta, Brij Mohan; Zargar, Samir H.; Arora, Manu; Tandon, Vishal R.

    2016-01-01

    Aim and Objective: To compare efficacy and safety of escitalopram with desvenlafaxine in the treatment of major depression. Materials and Methods: A total of 60 patients of depression were randomized into two groups after meeting inclusion criterion. In the first 3 weeks, escitalopram 10 mg/day was given and then 20 mg/day for the next 3 weeks in group 1 (n = 30). Desvenlafaxine in the first 3 weeks was given 50 mg/day and 100 mg/day for the next 3 weeks in group 2 (n = 30). The parameters evaluated during the study were efficacy assessments byHamilton Scale of Rating Depression (HAM-D), Hamilton Rating Scale of Anxiety (HAM-A), and Clinical Global Impression (CGI). Safety assessments were done by UKU-scale. Results: Escitalopram and desvenlafaxine significantly (P < 0.001), reduced HAM-D, HAM-A, and CGI scores from their respective base lines. However, on comparison failed show any statistical difference at 3 and 6 weeks of treatment. Escitalopram and desvenlafaxine were both found to be safe and well-tolerated and there was not much difference between the two groups as evident from UKU Scale and their effect on various biochemical parameters. Conclusion: The present study demonstrated similar efficacy and safety in reducing depression and anxiety with both escitalopram and desvenlafaxine, but clinical superiority of one drug over the other cannot be concluded due to limitations of the small sample size. PMID:26955576

  13. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

    PubMed Central

    Berlant, Jeffrey L

    2004-01-01

    Background In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD) observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD. Methods Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female) with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5) or augmentation (n = 28). The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C) score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms. Results For those taking the PCL-C at both baseline and week 4 (n = 30), total symptoms declined by 49% at week 4 (paired t-test, P < 0.001) with similar subscale reductions for reexperiencing, avoidance/numbing, and hyperarousal symptoms. The response rate at week 4 was 77%. Age, sex, bipolar comorbidity, age at onset of PTSD, duration of symptoms, severity of baseline PCL-C score, and monotherapy versus add-on medication administration did not predict reduction in PTSD symptoms. Median time to full response was 9 days and median dosage was 50 mg/day. Conclusions Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials. PMID:15315714

  14. Escitalopram in the treatment of patients with schizophrenia and obsessive-compulsive disorder: an open-label, prospective study.

    PubMed

    Stryjer, Rafael; Dambinsky, Yael; Timinsky, Igor; Green, Tamar; Kotler, Moshe; Weizman, Abraham; Spivak, Baruch

    2013-03-01

    The current data suggest that up to 50% of patients with schizophrenia have obsessive-compulsive (OC) symptoms coexisting with psychosis and between 7.8 and 46% of schizophrenia patients also have full-blown obsessive-compulsive disorder (OCD). The aim of this study was to examine the efficacy of the most selective serotonin reuptake inhibitor escitalopram in the management of OCD in schizophrenia patients. The study was an open-label prospective trial of 12 weeks' duration in which escitalopram at a dose of up to 20 mg/day was added to the existing antipsychotic drug regimen in schizophrenia patients with OCD. Fifteen patients (10 men/five women) with the diagnosis of schizophrenia and OCD were recruited for the study (mean age: 39±14, range 21-61 years) and received escitalopram according to the study design. A significant improvement was observed in the total Yale Brown Obsessive-Compulsive Scale (Y-BOCS) scores and in the scores of both the Y-BOCS-Obsession and the Y-BOCS-Compulsion subscale at the end point. In addition, a significant improvement was observed in the total scores of the Positive and Negative Syndrome Scale and particularly in scores of anxiety, tension, depression, and preoccupation items. No adverse effects of escitalopram were reported by patients during the trial. In our prospective 12-week open-label study, escitalopram 20 mg/day was well tolerated and improved OC symptoms in schizophrenia patients. Our preliminary results are encouraging and a double-blind randomized study is required to confirm our results.

  15. The effects of amisulpride on five dimensions of psychopathology in patients with schizophrenia: a prospective open- label study

    PubMed Central

    Herrera-Estrella, Miguel; Apiquian, Rogelio; Fresan, Ana; Sanchez-Torres, Isabel

    2005-01-01

    Background The efficacy of antipsychotics can be evaluated using the dimensional models of schizophrenic symptoms. The D2/D3-selective antagonist amisulpride has shown similar efficacy and tolerability to other atypical antipsychotics. The aim of the present study was to determine the efficacy of amisulpride on the dimensional model of schizophrenic symptoms and tolerability in latin schizophrenic patients. Method Eighty schizophrenic patients were enrolled and 70 completed a prospective open-label 3-month study with amisulpride. The schizophrenic symptoms, psychosocial functioning and side-effects were evaluated with standardized scales. Results The patients showed significant improvement in the five dimensions evaluated. Amisulpride (median final dose 357.1 mg/d) was well-tolerated without treatment-emergent extrapyramidal side-effects. Conclusion Amisulpride showed efficacy on different psychopathological dimensions and was well tolerated, leading to consider this drug a first line choice for the treatment of schizophrenia. PMID:15869707

  16. Ren Shen Yangrong Tang for Fatigue in Cancer Survivors: A Phase I/II Open-Label Study

    PubMed Central

    Xu, Yichen; Chen, Yanzhi

    2015-01-01

    Abstract Objectives: This open-label, prospective, phase I/II trial was performed to establish the safety and efficacy of Traditional Chinese Medicine (TCM) herbal products for treating non–anemia-related fatigue in patients with cancer. Although this practice is widespread in China, it has not been confirmed in a prospective clinical study. Design: Thirty-three patients who had completed cancer treatment, had stable disease and no anemia, and reported moderate to severe fatigue (rated ≥4 on a 0–10 scale) were enrolled in a TCM outpatient clinic. Patients took Ren Shen Yangrong Tang (RSYRT) decoction, a soup containing 12 TCM herbs, twice a day for 6 weeks. RSYRT aims to correct qi deficiency. Fatigue was assessed before and after RSYRT therapy, which all patients completed. Results: No discomfort or toxicity was observed. Before the study, all patients had had fatigue for at least 4 months. Fatigue severity decreased significantly from before therapy to 6 weeks after therapy: from 7.06 to 3.30 on a 0–10 scale (p<0.001). Fatigue category (mild, moderate, severe) shifted significantly (p=0.024): Of 22 patients with severe fatigue (rated ≥7) before therapy, 11 had mild fatigue and 11 had moderate fatigue after TCM treatment. The time-to-fatigue-alleviation was 2–3 weeks. Conclusion: RSYRT therapy was safe and was associated with fatigue improvement in nonanemic cancer survivors, consistent with historical TCM clinical practice experience. Because of a possible placebo effect in this open-label study, decoction RSYRT warrants further study in randomized clinical trials to confirm its effectiveness for managing moderate to severe fatigue. PMID:25918996

  17. Ramelteon for Insomnia Symptoms in a Community Sample of Adults with Generalized Anxiety Disorder: An Open Label Study

    PubMed Central

    Gross, Paul K.; Nourse, Rosemary; Wasser, Thomas E.

    2009-01-01

    Objective: Prior research confirms the relationship between insomnia and psychiatric disorders, particularly anxiety and depression. The effectiveness and tolerability of ramelteon was examined in adult generalized anxiety disorder (GAD) patients with insomnia symptoms. Methods: Twenty-seven adults with sleep disturbance meeting DSM-IV diagnostic criteria for GAD and partially responsive on an SSRI or SNRI by randomization visit (as signified by a Hamilton Anxiety scale [HAMA] maximum score of 15 and minimum of 8, Clinical Global Impressions Severity of Illness [CGI-S] scale of ≤ 4 and ≥ 2 [measuring anxiety symptoms], CGI-S of ≥ 4 [measuring insomnia symptoms], ≥ 5 on the Pittsburgh Sleep Quality Index [PSQI], and ≥ 10 on the Epworth Sleepiness Scale [ESS]) were treated openly for 10 weeks on ramelteon 8 mg at bedtime. Analysis was conducted using repeated measures methodology. Patient reported sleep diaries were maintained throughout the study. Results: Significant symptom reduction was observed on all scales (HAMA, ESS, CGI-I, CGI-S), with subjects falling asleep faster and sleeping longer. Headache upon stopping ramelteon, daytime tiredness, agitation, and depression were the most commonly reported side effects and were cited as transient. Conclusion: Data from this 12-week open-label study suggests ramelteon is an effective and generally well tolerated treatment for insomnia symptoms in this community sample of adults with GAD. Citation: Gross PK; Nourse R; Wasser TE. Ramelteon for insomnia symptoms in a community sample of adults with generalized anxiety disorder: an open label study. J Clin Sleep Med 2009;5(1):28–33. PMID:19317378

  18. Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

    PubMed Central

    Sasaki, Tsuyoshi; Hashimoto, Kenji; Tachibana, Masumi; Kurata, Tsutomu; Okawada, Keiko; Ishikawa, Maki; Kimura, Hiroshi; Komatsu, Hideki; Ishikawa, Masatomo; Hasegawa, Tadashi; Shiina, Akihiro; Hashimoto, Tasuku; Kanahara, Nobuhisa; Shiraishi, Tetsuya; Iyo, Masaomi

    2014-01-01

    Background Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine) has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK)-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD) symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD. Subjects and methods This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0) received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS), Japanese version, and the Das–Naglieri Cognitive Assessment System (DN-CAS), Japanese version. Results A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores) improved significantly (P<0.001). Furthermore, a comparison of baseline DN-CAS total scores and 4-week end-point scores showed a mild trend of improvement (P=0.093). Tipepidine was well tolerated, with no patients discontinuing medication because of side effects. Conclusion Our pilot study suggests that tipepidine therapy may prove to be an effective alternative treatment for pediatric patients with ADHD. Nonetheless, more detailed randomized, double-blind trials are needed to confirm tipepidine’s efficacy

  19. Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

    ERIC Educational Resources Information Center

    Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

    2013-01-01

    Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found…

  20. An open-label pilot study of quetiapine plus mirtazapine for heavy drinkers with alcohol use disorder.

    PubMed

    Brunette, Mary F; Akerman, Sarah C; Dawson, Ree; O'Keefe, Christopher D; Green, Alan I

    2016-06-01

    Animal research suggests that medications that produce a weak dopamine D2 receptor blockade and potentiate noradrenergic activity may decrease alcohol drinking. In an open-label pilot study of subjects with alcohol dependence, we tested whether the combination of quetiapine, a weak dopamine D2 receptor antagonist, whose primary metabolite, desalkylquetiapine, is a norepinephrine reuptake inhibitor, and mirtazapine, a potent α2 norepinephrine receptor antagonist, would decrease alcohol drinking and craving. Twenty very heavy drinkers with alcohol dependence entered a trial of 8 weeks of treatment with quetiapine followed by 8 weeks of treatment with a combination of quetiapine plus mirtazapine. Alcohol use was assessed weekly with a Timeline Follow-Back interview and craving with the Penn Alcohol Craving Scale. Among the 11 completers, subjects reported improved outcomes in the quetiapine plus mirtazapine period compared to the quetiapine alone period: fewer very heavy drinking days per week (1.3 [SD = 2.4] vs. 2.1 [SD = 2.8]; t = 2.3, df = 10, p = 0.04); fewer total number of drinks per week (39.7 [SD = 61.6] vs. 53.4 [SD = 65.0]; t = 2.8, df = 10, p = 0.02); and lower craving scores (2.5 [SD = 1.4] vs. 3.2 [SD = 1.2]; t = 2.4, df = 10, p = 0.04). All subjects reported at least one adverse event; 72.7% reported somnolence. In this open-label pilot study, treatment with quetiapine plus mirtazapine was associated with a decrease in alcohol drinking and craving. These findings are consistent with our previous work in animal models of alcohol use disorders and suggest that further study of medications or combinations of medications with this pharmacologic profile is warranted.

  1. Pharmacokinetics, pharmacodynamics, and safety of pasireotide LAR in patients with acromegaly: a randomized, multicenter, open-label, phase I study.

    PubMed

    Petersenn, Stephan; Bollerslev, Jens; Arafat, Ayman M; Schopohl, Jochen; Serri, Omar; Katznelson, Laurence; Lasher, Janet; Hughes, Gareth; Hu, Ke; Shen, George; Reséndiz, Karina Hermosillo; Giannone, Vanessa; Beckers, Albert

    2014-11-01

    Pasireotide (SOM230), a multireceptor-targeted somatostatin analogue, has exhibited favorable safety/tolerability in several clinical studies. A long-acting-release (LAR) formulation of pasireotide may offer advantages over the subcutaneous formulation. This randomized, open-label, Phase I study evaluated the safety, PK, and PD of pasireotide LAR 20, 40, or 60 mg/month in patients with acromegaly. Safety assessments and blood samples for PK and PD were taken at designated time points. Thirty-five patients were randomized and completed the study. Steady-state pasireotide concentrations were achieved following three monthly injections. Trough pasireotide concentrations (ng/mL) 28 days after each injection were: 2.48, 4.16, and 3.10 (20 mg group); 6.42, 6.62, and 7.12 (40 mg group); and 9.51, 11.7, and 13.0 (60 mg group). At study end, 51% and 57% of patients achieved GH levels ≤2.5 μg/L and IGF-1 levels below ULN, respectively. Compared with baseline, fasting blood glucose and HbA1c levels increased, whereas fasting blood insulin levels decreased. Acromegaly symptoms were generally improved. Adverse events were mostly gastrointestinal and mild/moderate. Pasireotide LAR was generally well tolerated. Steady-state PK was achieved after three monthly doses; exposures were approximately dose proportional. Control of GH, IGF-1, and symptoms improved, suggesting that pasireotide LAR may be an effective treatment for acromegaly.

  2. Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

    PubMed Central

    Libove, Robin A.; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y.

    2014-01-01

    The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD. PMID:24849255

  3. Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder.

    PubMed

    Fung, Lawrence K; Libove, Robin A; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y

    2014-11-01

    The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD.

  4. The 5-HT1D receptor agonist zolmitriptan for neuroleptic-induced akathisia: an open label preliminary study.

    PubMed

    Gross-Isseroff, Ruth; Magen, Ayelet; Shiloh, Roni; Hermesh, Haggai; Weizman, Abraham

    2005-01-01

    Neuroleptic-induced akathisia (NIA) is a common, sometimes incapacitating, adverse side-effect of antipsychotic drugs (APDs). Several non-selective post-synaptic 5-HT2 blockers have shown a beneficial antiakathisic effect. We hypothesized that selective stimulation of the presynaptic 5-HT1D serotonergic inhibitory autoreceptor could also be beneficial in NIA. The study group included eight schizophrenia inpatients with acute or chronic NIA who were treated with unchanged doses of APDs. Participants received, in an open-labelled design, 7.5 mg/day of zolmitriptan (selective 5-HT1D agonist) for 3 consecutive days. Positive and Negative Syndrome Scale and Barnes akathisia scale (BAS) scores were monitored before and at the end of the study. BAS score decreased by 5.25 points following zolmitriptan administration (9.0+/-2.27 to 3.75+/-2.55, t=6.1, d.f.=7, P=0.0005). In one case, the BAS score dropped from a 3-year score >or=9 points (while relatively non-responsive to numerous antiakathisic agents) to 4 points at endpoint. In conclusion, zolmitriptan appears to exert significant and rapid beneficial antiakathisic effect, even in chronic and resistant NIA. Larger, long-term, double-blind, placebo- and comparator- (e.g. propranolol) controlled studies are required to substantiate the efficacy, safety and tolerability of zolmitriptan, as well as the role of serotonergic neurotransmission in NIA.

  5. Bupropion for interferon-alpha-induced depression in patients with hepatitis C viral infection: an open-label study.

    PubMed

    Chen, Wei-Chun; Lai, Hsueh-Chou; Su, Wen-Pang; Palani, Mahalakshmi; Su, Kuan-Pin

    2015-01-01

    Interferon (IFN)-α therapy for chronic hepatitis C virus (HCV) infection is frequently associated with major depressive episodes. Bupropion, a commonly used antidepressant agent, has recently found to have strong anti-inflammatory effects in animal models. Despite of the theoretical relevancy, the antidepressant effect of bupropion in IFN-alpha-induced depression has never been studied. Ten HCV patients with IFN-α-induced depression were recruited to receive 8-week bupropion treatment and were assessed every 2 weeks for depressive symptoms by the Hamilton rating scale for depression (HAMD) and somatic symptoms by the Neurotoxicity Rating Scale (NRS). Four of the 10 patients met the criteria for remission (total HAMD scores≤7), and 5 patients met the criteria for response (at least 50% reduction in total HAMD scores). In addition, 5 patients had 50% decreases in NRS for neuropsychiatric symptoms. This preliminary open-label study suggests that bupropion is effective in treating IFN-alpha-induced depressive and somatic symptoms.

  6. A Phase 4, Pilot, Open-Label Study of VIVITROL® (Extended-Release Naltrexone XR-NTX) for Prisoners.

    PubMed

    Gordon, Michael S; Kinlock, Timothy W; Vocci, Frank J; Fitzgerald, Terrence T; Memisoglu, Asli; Silverman, Bernard

    2015-12-01

    This was a Phase 4, pilot, open-label feasibility study of extended-release injectable naltrexone (XR-NTX) administered to pre-release prisoners having a history of pre-incarceration opioid disorder. We evaluated the relationship between XR-NTX adherence and criminal recidivism (re-arrest and re-incarceration) and opioid and cocaine use. Twenty-seven pre-release male and female prisoners who had opioid disorders during the year prior to index incarceration were recruited and received one XR-NTX injection once each month for 7 months (1 injection pre-release from prison and 6 injections in the community) and of those 27, 10 (37%) were retained in treatment at 7-months post release. Results indicate those completing 6 compared to those completing <6 injections were less likely to test positive for opioids in the community (0% vs. 62.5%, respectively; p=0.003). Although not statistically significant, individuals who did not complete all 6 injections were more likely to be re-arrested compared to those completing all 6 community injections (31.3% vs. 0%, respectively; p=0.123). Contingent upon further study of a randomized controlled trial, XR-NTX may be a feasible option in the prison setting in view of the lack of potential for diversion. Furthermore, these data suggest that completing the entire course of treatment (6 injections) may reduce opioid use and, to a lesser degree, re-arrest and re-incarceration. PMID:26299956

  7. Effect of topical vitamin D on chronic kidney disease-associated pruritus: An open-label pilot study.

    PubMed

    Jung, Kyung Eun; Woo, Yu Ri; Lee, Joong Sun; Shin, Jong Ho; Jeong, Jin Uk; Koo, Dae Won; Bang, Ki Tae

    2015-08-01

    Chronic kidney disease-associated pruritus (CKD-aP) is a troublesome symptom in patients with end-stage renal disease (ESRD). Recently, vitamin D deficiency has been known to be one of the possible etiologic factors in CKD-aP. However, limited data is available on whether topical vitamin D treatment is effective for relieving CKD-aP. Therefore, the purpose of this study is to evaluate the effectiveness of topically vitamin D for CKD-aP. Twenty-three patients with CKD-aP were enrolled in a single center, open-label study. Patients were instructed to apply a topical vitamin D (calcipotriol) agent (Daivonex solution; LEO Pharma) or vehicle solution twice daily for a month. We assessed the efficacy and safety of topical vitamin D on CKD-aP using clinical and dermoscopic photographs, and questionnaires including the validated modified pruritus assessment score (VMPAS) and visual analog scale (VAS) every 2 weeks. Dry dermoscopic findings showed significant improvement of scale (dryness) on the skin of topical vitamin D-treated patients compared with those of the vehicle group. Both VMPAS and VAS were significantly decreased after 2 and 4 weeks of the topical vitamin D treatment compared with the vehicle, respectively (P < 0.05). No significant side-effects were observed. Topical vitamin D may be one of the safe and effective therapeutic candidates for CKD-aP.

  8. A Prospective, Open-Label Study of Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

    SciTech Connect

    Kamstrup, Maria R.; Specht, Lena; Skovgaard, Gunhild L.; Gniadecki, Robert

    2008-07-15

    Purpose: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. Methods and Materials: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4 fractions over 4 successive days. Results: Two patients had a complete clinical response but relapsed after 3.5 months. Six patients had partial clinical responses, with a mean duration of 2.0 months. One patient had no clinical response. Median time to relapse was 2.7 months. One patient died of unrelated causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. Conclusion: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration of remission is short. Low-dose total skin electron beam therapy may find application in palliative treatment of mycosis fungoides because of limited toxicity and the possibility of repeating treatments for long-term disease control.

  9. An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity

    PubMed Central

    Liau, Kai Ming; Lee, Yeong Yeh; Chen, Chee Keong; Rasool, Aida Hanum G.

    2011-01-01

    Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans. PMID:22164340

  10. Onabotulinumtoxin A Treatment of Drooling in Children with Cerebral Palsy: A Prospective, Longitudinal Open-Label Study

    PubMed Central

    Møller, Eigild; Pedersen, Søren Anker; Vinicoff, Pablo Gustavo; Bardow, Allan; Lykkeaa, Joan; Svendsen, Pia; Bakke, Merete

    2015-01-01

    The aim of this prospective open-label study was to treat disabling drooling in children with cerebral palsy (CP) with onabotulinumtoxin A (A/Ona, Botox®) into submandibular and parotid glands and find the lowest effective dosage and least invasive method. A/Ona was injected in 14 children, Mean age 9 years, SD 3 years, under ultrasonic guidance in six successive Series, with at least six months between injections. Doses and gland involvement increased from Series A to F (units (U) per submandibular/parotid gland: A, 10/0; B, 15/0; C, 20/0; D, 20/20; E, 30/20; and F, 30/30). The effect was assessed 2, 4, 8, 12, and 20 weeks after A/Ona (drooling problems (VAS), impact (0–7), treatment effect (0–5), unstimulated whole saliva (UWS) flow and composition)) and analyzed by two-way ANOVA. The effect was unchanged–moderate in A to moderate–marked in F. Changes in all parameters were significant in E and F, but with swallowing problems ≤5 weeks in 3 of 28 treatments. F had largest VAS and UWS reduction (64% and 49%). We recommend: Start with dose D A/Ona (both submandibular and parotid glands and a total of 80 U) and increase to E and eventually F (total 120 U) without sufficient response. PMID:26134257

  11. Open-Label Study of Craving in Smokers With Schizophrenia Using Nicotine Nasal Spray Compared to Nicotine Patch

    PubMed Central

    Williams, Jill M.; Gandhi, Kunal K.; Karavidas, Maria Katsamanis; Steinberg, Marc L.; Lu, Shou-En; Foulds, Jonathan

    2009-01-01

    Rationale: Nicotine nasal spray (NNS) may be better for relieving acute cigarette cravings than other nicotine replacement and it may help smokers with schizophrenia because of its rapid onset of action. Objectives: We tested whether NNS was more effective than a nicotine patch (NP; 21 mg) in reducing cue-induced craving during a 3-day abstinence. Methods: Twenty-five smokers with schizophrenia or schizoaffective disorder (SA) were randomized to open-label NNS or NP treatment after baseline measures of craving were assessed. NNS users were instructed to dose at a minimum of 1/hour and up to a maximum of 40/day. Averages from a 4-item visual analogue scale (need, urge, want to smoke, crave a cigarette) measured craving. Results: Five subjects who smoked (4 NP, 1 NNS) were excluded, leaving 21 (11 NP, 10 NNS) for analyses. No differences were detected between groups on baseline craving. On day 3, NNS users reported significantly less craving in response to smoking cues compared to NP users (mean craving scores: NNS, 7.0; NP, 20.3; p = .014). A repeated measure ANCOVA demonstrated significantly reduced craving in the NNS group compared to the NP group from baseline to day 3 (F = 5.09; p = .037). NNS users took an average of 20 doses/day, and NNS was rated as being as easy to use as NP. Conclusions: The potential utility of NNS in smokers with schizophrenia supports the need for placebo-controlled studies. PMID:19763279

  12. The effects of QEEG-informed neurofeedback in ADHD: an open-label pilot study.

    PubMed

    Arns, Martijn; Drinkenburg, Wilhelmus; Leon Kenemans, J

    2012-09-01

    In ADHD several EEG biomarkers have been described before, with relevance to treatment outcome to stimulant medication. This pilot-study aimed at personalizing neurofeedback treatment to these specific sub-groups to investigate if such an approach leads to improved clinical outcomes. Furthermore, pre- and post-treatment EEG and ERP changes were investigated in a sub-group to study the neurophysiological effects of neurofeedback. Twenty-one patients with ADHD were treated with QEEG-informed neurofeedback and post-treatment effects on inattention (ATT), hyperactivity/impulsivity (HI) and comorbid depressive symptoms were investigated. There was a significant improvement for both ATT, HI and comorbid depressive complaints after QEEG-informed neurofeedback. The effect size for ATT was 1.78 and for HI was 1.22. Furthermore, anterior individual alpha peak frequency (iAPF) demonstrated a strong relation to improvement on comorbid depressive complaints. Pre- and post-treatment effects for the SMR neurofeedback sub-group exhibited increased N200 and P300 amplitudes and decreased SMR EEG power post-treatment. This pilot study is the first study demonstrating that it is possible to select neurofeedback protocols based on individual EEG biomarkers and suggests this results in improved treatment outcome specifically for ATT, however these results should be replicated in further controlled studies. A slow anterior iAPF at baseline predicts poor treatment response on comorbid depressive complaints in line with studies in depression. The effects of SMR neurofeedback resulted in specific ERP and EEG changes.

  13. Divalproex Sodium -ER in Outpatients with Disruptive Behavior Disorders: A Three Month Open Label Study

    ERIC Educational Resources Information Center

    Saxena, Kirti; Mora, Linda; Torres, Erika; Hall, Rebecca; Delizonna, Laura; Torres, Alex; Steiner, Hans

    2010-01-01

    This aim of this clinical trial was to study the effects of divalproex sodium (DVPX) in reducing Reactive/Affective/ Defensive/ Impulsive Aggression (RADI) in youth with Disruptive Behavior Disorders (DBD) in an outpatient clinic over a period of 3 months. We recruited forty participants with Oppositional Defiant Disorder or Conduct Disorder.…

  14. Autologous mesenchymal stem cell therapy in progressive multiple sclerosis: an open label study.

    PubMed

    Bonab, Mandana Mohyeddin; Sahraian, Mohammad Ali; Aghsaie, Aida; Karvigh, Sanaz Ahmadi; Hosseinian, Seyed Massoud; Nikbin, Behrouz; Lotfi, Jamshid; Khorramnia, Saeideh; Motamed, Mohammad Reza; Togha, Mansoureh; Harirchian, Mohammad Hossien; Moghadam, Nahid Beladi; Alikhani, Katayoun; Yadegari, Samira; Jafarian, Sirous; Gheini, Mohammad Reza

    2012-11-01

    Despite updating knowledge and a growing number of medications for multiple sclerosis (MS), no definite treatment is available yet for patients suffering from progressive forms of the disease. Autologous bone marrow derived mesenchymal stem cell (BM-MSC) transplantation is a promising method proposed as a therapy for MS. Although the safety of these cells has been confirmed in hematological, cardiac and inflammatory diseases, its efficacy in MS treatment is still under study. Patients with progressive MS (expanded disability status scale score: 4.0 -6.50) unresponsive to conventional treatments were recruited for this study. Twenty-five patients [f/m: 19/6, mean age: 34.7±7] received a single intrathecal injection of ex-vivo expanded MSCs (mean dose: 29.5×10(6) cells). We observed their therapeutic response for 12 months. Associated short-term adverse events of injection consisted of transient low-grade fever, nausea /vomiting, weakness in the lower limbs and headache. No major delayed adverse effect was reported. 3 patients left the study for personal reasons. The mean (SD) expanded disability status scale (EDSS) score of 22 patients changed from 6.1 (0.6) to 6.3 (0.4). Clinical course of the disease (measured by EDSS) improved in 4, deteriorated in 6 and had no change in 12 patients. In MRI evaluation, 15 patients showed no change, whereas 6 patients showed new T2 or gadolinium enhanced lesions (1 lost to follow-up). It seems that MSC therapy can improve/stabilize the course of the disease in progressive MS in the first year after injection with no serious adverse effects. Repeating the study with a larger sample size, booster injections and longer follow-up using a controlled study design is advised. PMID:23061813

  15. Open-Label, Long-Term Safety Study of Cevimeline in the Treatment of Postirradiation Xerostomia

    SciTech Connect

    Chambers, Mark S. Jones, Christopher Uwe; Biel, Merrill A.; Weber, Randal S.; Hodge, Kenneth M.; Chen, Y.; Holland, John M.; Ship, Jonathan; Vitti, Robert; Armstrong, Ingrid; Garden, Adam S.; Haddad, Robert

    2007-12-01

    Purpose: To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. Methods and Materials: A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). Results: Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). Conclusions: Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region.

  16. An open label study on the supplementation of Gymnema sylvestre in type 2 diabetics.

    PubMed

    Kumar, Smriti Nanda; Mani, Uliyar Vitaldas; Mani, Indirani

    2010-09-01

    Diabetes mellitus is a complex metabolic disorder characterized by chronic hyperglycemia, and associated with long-term damage and dysfunction of various organs. Management of diabetes is therefore vital and involves maintaining euglycemia as much as possible by reducing blood glucose and by increasing insulin sensitivity and peripheral glucose uptake. Ayurveda has promoted the management of diabetes by regulating carbohydrate metabolism using several medicinal herbs, one of which is Gymnema sylvestre (GS). GS has been used in parts of India as a hypoglycemic agent and the results have been encouraging. Accordingly, we planned a quasi-experimental study to investigate the efficacy of the herb among type 2 diabetics. Patients enrolled from free-living population were purposively assigned to experimental or control groups, based on their willingness to participate in the study. The experimental group was supplemented with 500 mg of the herb per day for a period of 3 months, and the efficacy of the herb was assessed through a battery of clinical and biochemical tests. Supplementation of the diet with GS reduced polyphagia, fatigue, blood glucose (fasting and post-prandial), and glycated hemoglobin and there was a favorable shift in lipid profiles and in other clinico-biochemical tests. These findings suggest a beneficial effect of GS in the management of diabetes mellitus.

  17. An open label study on the supplementation of Gymnema sylvestre in type 2 diabetics.

    PubMed

    Kumar, Smriti Nanda; Mani, Uliyar Vitaldas; Mani, Indirani

    2010-09-01

    Diabetes mellitus is a complex metabolic disorder characterized by chronic hyperglycemia, and associated with long-term damage and dysfunction of various organs. Management of diabetes is therefore vital and involves maintaining euglycemia as much as possible by reducing blood glucose and by increasing insulin sensitivity and peripheral glucose uptake. Ayurveda has promoted the management of diabetes by regulating carbohydrate metabolism using several medicinal herbs, one of which is Gymnema sylvestre (GS). GS has been used in parts of India as a hypoglycemic agent and the results have been encouraging. Accordingly, we planned a quasi-experimental study to investigate the efficacy of the herb among type 2 diabetics. Patients enrolled from free-living population were purposively assigned to experimental or control groups, based on their willingness to participate in the study. The experimental group was supplemented with 500 mg of the herb per day for a period of 3 months, and the efficacy of the herb was assessed through a battery of clinical and biochemical tests. Supplementation of the diet with GS reduced polyphagia, fatigue, blood glucose (fasting and post-prandial), and glycated hemoglobin and there was a favorable shift in lipid profiles and in other clinico-biochemical tests. These findings suggest a beneficial effect of GS in the management of diabetes mellitus. PMID:22432517

  18. Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study.

    PubMed

    Bradstreet, James Jeffrey; Sych, Nataliia; Antonucci, Nicola; Klunnik, Mariya; Ivankova, Olena; Matyashchuk, Irina; Demchuk, Mariya; Siniscalco, Dario

    2014-01-01

    Autism spectrum disorders (ASDs) are heterogeneous complex neurodevelopmental pathologies defined by behavioral symptoms, but which have well-characterized genetic, immunological, and physiological comorbidities. Despite extensive research efforts, there are presently no agreed upon therapeutic approaches for either the core behaviors or the associated comorbidities. In particular, the known autoimmune disorders associated with autism are appealing targets for potential stem cell therapeutics. Of the various stem cell populations, fetal stem cells (FSCs) offer the potent immunoregulatory functions found in primordial mesenchymal stem cells, while exhibiting rapid expansion capacity and recognized plasticity. These properties enhance their potential for clinical use. Furthermore, FSCs are potent and implantable "biopharmacies" capable of delivering trophic signals to the host, which could influence brain development. This study investigated the safety and efficacy of FSC transplantations in treating children diagnosed with ASDs. Subjects were monitored at pre, and then 6 and 12 months following the transplantations, which consisted of two doses of intravenously and subcutaneously administered FSCs. The Autism Treatment Evaluation Checklist (ATEC) test and Aberrant Behavior Checklist (ABC) scores were performed. Laboratory examinations and clinical assessment of adverse effects were performed in order to evaluate treatment safety. No adverse events of significance were observed in ASD children treated with FSCs, including no transmitted infections or immunological complications. Statistically significant differences (p < 0.05) were shown on ATEC/ABC scores for the domains of speech, sociability, sensory, and overall health, as well as reductions in the total scores when compared to pretreatment values. We recognize that the use of FSCs remains controversial for the present. The results of this study, however, warrant additional investigations into the mechanisms

  19. Effects of probiotic Lactobacillus brevis KB290 on incidence of influenza infection among schoolchildren: an open-label pilot study

    PubMed Central

    Waki, N; Matsumoto, M; Fukui, Y; Suganuma, H

    2014-01-01

    Abstract We investigated the efficacy of dietary consumption of Lactobacillus brevis KB290 (KB290) against influenza in humans by a preliminary intervention study on elementary schoolchildren, using a commercially available probiotic drink. Subjects were divided into Groups A and B, and an open-label, parallel-group trial was conducted in two 8-week periods at a 1-month interval in winter 2013/2014. Group A was provided with a bottle of the test drink containing KB290 (about 6 billion colony-forming units) every school day in the first period and had no treatment in the second period, and vice versa for Group B. Epidemic influenza was not observed during the first period and only two of 1783 subjects were diagnosed. In the second period, the incidence of influenza in Groups A (no treatment) and B (provided the test drink) was 23·9 and 15·7%, respectively, and the difference was statistically significant (P < 0·001). The reduction in the incidence of influenza by KB290 consumption was especially remarkable in unvaccinated individuals. This is believed to be the first study to show a probiotic food reducing the incidence of influenza in schoolchildren, although further studies are needed to confirm the effectiveness of the probiotic strain KB290. Significance and Impact of the Study We demonstrated a reduction in the incidence of influenza in 1089 schoolchildren by continual intake of a probiotic drink containing Lactobacillus brevis KB290 (KB290), isolated from a traditional Japanese pickle ‘Suguki’. The effect was especially evident in subjects not inoculated with influenza vaccine. This is believed to be the first report to show reduced incidence of influenza in schoolchildren taking a probiotic food. Further studies are needed to confirm the effectiveness of the probiotic strain KB290, which may be useful in the development of potential anti-influenza agents derived from common foods. PMID:25294223

  20. Agomelatine versus Sertraline: An Observational, Open-labeled and 12 Weeks Follow-up Study on Efficacy and Tolerability

    PubMed Central

    Akpınar, Esma; Cerit, Cem; Talas, Anıl; Tural, Ümit

    2016-01-01

    Objective In this open-labeled, 12 weeks follow-up study, we aimed to compare the efficacy and tolerability of agomelatine with sertraline Methods The outpatients of adult psychiatry clinic who have a new onset of depression and diagnosed as ‘major depressive episode’ by clinician according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition and prescribed agomelatine (25 mg/day) or sertraline (50 mg/day) were included in the study. Results The decline of mean Montgomery-Asberg Depression Rating Scale (MADRS) scores of agomelatine group was significantly higher than the sertraline group at the end of 2nd week; however, the difference was not significant at the end of 3 months. Mean Clinical Global Impression-Improvement scale (CGI-I) scores of agomelatine group was lower than sertraline group at first week. Mean CGI-Severity scale and CGI-I scores were favour to sertraline group at the end of the study. Remission rates were 46.7% for sertraline group and 33.3% for agomelatine group while response rates were 76.7% for both groups. Any patient from agomelatine group dropped-out due to adverse effects. The amount of side effects was also less with agomelatine. Conclusion Agomelatine has a rapid onset efficacy on depressive symptoms and this can be beneficial for some critical cases. Considering MADRS scores, agomelatine seems to have similar efficacy with sertraline but we also point the need for long term studies since CGI scores were favour to sertraline group at the end of the study. Agomelatine has a favourable tolerability profile both in terms of discontinuation and the amount of side effects compared to sertraline. PMID:27776387

  1. A prospective, open-label study to evaluate symptomatic remission in schizophrenia with risperidone long-acting injectable in Korea.

    PubMed

    Lee, Nam Young; Kim, Se Hyun; Cho, Seong Jin; Chung, Young-Cho; Jung, In Kwa; Kim, Chang Yoon; Kim, Duk Ho; Lee, Dong Geun; Lee, Yo Han; Lim, Weon Jeong; Na, Young Suk; Shin, Sang Eun; Woo, Jong-Min; Yoon, Jin Sang; Yoon, Bo-Hyun; Ahn, Yong Min; Kim, Yong Sik

    2014-09-01

    This study was designed to investigate long-term clinical outcomes of risperidone long-acting injectable (RLAI) in patients with schizophrenia or schizoaffective disorder. An open-label, 48-week, prospective study of RLAI treatment was carried out at 63 centers in South Korea. Initial and maintenance dosage of RLAI were adjusted according to clinical judgment. Efficacy was measured by the remission rate, continuation rate, and changes in the clinical measurements such as eight items of the Positive and Negative Symptom Scale (PANSS), the Clinical Global Impression - Severity, and the Schizophrenia Quality of Life Scale. In terms of the safety, Simpson-Angus rating Scale, adverse events (AEs), and BMI were investigated. Of the 522 patients who were enrolled, 472 patients who had been assessed on the eight items of PANSS at baseline and at least once during RLAI treatment were included in the intention-to-treat (ITT) population. The per-protocol (PP) population included 184 patients (39.0%), who completed all assessments during 48 weeks of the follow-up period. Total scores of eight items of PANSS, Clinical Global Impression - Severity, and Schizophrenia Quality of Life Scale were reduced significantly from baseline to endpoint in both ITT and PP populations. The mean dose (SD) of RLAI was 33.2 (7.6) mg. In the PP population, the number of patients who scored 1-3 on eight items of PANSS were 47 (25.5%) at baseline and 144 (78.3%) at 48 weeks. According to the remission defining as scores 1-3 on eight items of PANSS sustaining of at least 6 months' duration by Andreasen, the numbers of patients who achieved remission were 45 (24.5%) at 24 weeks and 120 (65.2%) at 48 weeks. A significant decrease in the mean score of Simpson-Angus rating Scale and a significant increase in BMI over time in last observation carried forward were observed, and patients who fulfilled the remission criteria during the study showed more weight gain than those who did not. During the study

  2. An open-label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America.

    PubMed

    Nucci, Marcio; Colombo, Arnaldo L; Petti, Marco; Magana, Martin; Abreu, Paula; Schlamm, Haran T; Sanchez, Sonia P

    2014-01-01

    Incidence and mortality of candidaemia/invasive candidiasis (C/IC) is relatively high in Latin America versus North America and Europe. To assess efficacy and safety of intravenous (IV) anidulafungin in Latin American adults with documented C/IC. All patients in this open-label study received initial IV anidulafungin with optional step-down to oral voriconazole after 5 days; total treatment duration was 14-42 days. The primary endpoint was global response (clinical + microbiological response) at end of treatment (EOT); missing/indeterminate responses were failures. The study enrolled 54 patients; 44 had confirmed C/IC within 96 h before study entry and comprised the modified intent-to-treat population. Global response at EOT was 59.1% (95% CI: 44.6, 73.6), with 13 missing/indeterminate assessments. Thirty-day all-cause mortality was 43.1%. Fourteen patients (31.8%) were able to step-down to oral voriconazole; these patients had lower baseline acute physiological assessment and chronic health evaluation (APACHE) II scores and were less likely to have solid tumours or previous abdominal surgery. Anidulafungin was generally well tolerated with few treatment-related adverse events. Anidulafungin was associated with relatively low response rates influenced by a high rate of missing/indeterminate assessments and mortality comparable to other recent candidaemia studies in Latin America. In a subset of patients with lower APACHE II scores, short-course anidulafungin followed by oral voriconazole was successful.

  3. A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex

    PubMed Central

    Myers, Stephen P; O’Connor, Joan; Fitton, J Helen; Brooks, Lyndon; Rolfe, Margaret; Connellan, Paul; Wohlmuth, Hans; Cheras, Phil A; Morris, Carol

    2011-01-01

    Background: Isolated fucoidans from brown marine algae have been shown to have a range of immune-modulating effects. This exploratory study aimed to determine whether a seaweed nutrient complex containing a blend of extracts from three different species of brown algae plus nutrients is safe to administer and has biological potential as an immune modulator. The study was undertaken as an open-label combined Phase I and II study. Methods: Participants (n = 10) were randomized to receive the study medication at either a 100 mg (n = 5) or 1000 mg (n = 5) dose over 4 weeks. The primary outcome measurement was in vivo changes in lymphocyte subsets. The secondary outcome measures were ex vivo changes in T-lymphocyte (CD4 and CD8) activation, phagocytosis of granulocytes and monocytes, T helper 1/T helper 2 cytokines, and serum oxygen radical absorbance capacity. Results: The preparation was found to be safe over the 4 weeks at both doses tested. There were no clinically relevant changes to blood measurements of hemopoietic, hepatic, or renal function. Immunomodulatory measurements showed no dose response between the two doses. The combined results from the two doses demonstrated a significant increase in cytotoxic T cell numbers and phagocytic capacity in monocytes, and a significant decrease in levels of the inflammatory cytokine interleukin 6. A separate analysis of the 100 mg dose (n = 5) alone showed a significant linear component over time (P < 0.05) for phagocytosis by both granulocytes and monocytes. Conclusion: The seaweed nutrient complex was safe to use when taken orally over 4 weeks. The preparation was demonstrated to have potential as an immune modulator, and this bioactivity deserves further exploration. PMID:21383915

  4. Treatment of snoring and obstructive sleep apnea with a mandibular protruding device: an open-label study.

    PubMed

    Fransson, A M; Isacsson, G; Leissner, L C; Näsman, A B; Alton, M K

    2001-01-01

    The study objectives were to describe the changes in signs and symptoms of obstructive sleep apnea (OSA) and snoring using a mandibular protruding device (MPD) and to define the group of responders. The design of the study was a nonrandomized, open-labeled, prospective clinical study with a duration of 6 months. The setting was a hospital sleep laboratory and an ear, nose, and throat and dental outpatient clinic. Patients included 35 individuals treated: 22 with a diagnosis of OSA and 13 who snored without apnea. The intervention before MPD prescription entailed a medical examination, a one-night somnographic registration, a questionnaire, and a clinical jaw function examination. All procedures were iterated at the 6-month follow-up. When the patients used the MPD, the subjective symptoms decreased significantly (p < 0.001). Twenty-four of the 35 patients were classified as responders, i.e., reduced their symptoms > or = 50%. In the groups of OSA patients, the mean peak intensity of the snoring sound decreased from 71.6 dB to 62.0 dB (p < 0.001) and in the group of snorers, from 63.5 dB to 57.5 dB (p < 0.05). Eighteen of the 22 OSA patients decreased their ODI values by > or = 50% (responders). The mean ODI decreased from 15.4 to 3.5 (p < 0.001) and the blood oxygen saturation, SaO(2) nadir, increased from mean 81.9 to 85.7 (n.s.). Most patients with tongue base hyperplasia were classified as responders to the MPD treatment. In conclusion, a 6-month perspective shows that the MPD could be an effective treatment in reducing signs and symptoms of OSA and/or snoring, the compliance was acceptable and only minor adverse events occurred.

  5. Nutritional route in oesophageal resection trial II (NUTRIENT II): study protocol for a multicentre open-label randomised controlled trial

    PubMed Central

    Berkelmans, Gijs H K; Wilts, Bas J W; Kouwenhoven, Ewout A; Kumagai, Koshi; Nilsson, Magnus; Weijs, Teus J; Nieuwenhuijzen, Grard A P; van Det, Marc J; Luyer, Misha D P

    2016-01-01

    Introduction Early start of an oral diet is safe and beneficial in most types of gastrointestinal surgery and is a crucial part of fast track or enhanced recovery protocols. However, the feasibility and safety of oral intake directly following oesophagectomy remain unclear. The aim of this study is to investigate the effects of early versus delayed start of oral intake on postoperative recovery following oesophagectomy. Methods and analysis This is an open-label multicentre randomised controlled trial. Patients undergoing elective minimally invasive or hybrid oesophagectomy for cancer are eligible. Further inclusion criteria are intrathoracic anastomosis, written informed consent and age 18 years or older. Inability for oral intake, inability to place a feeding jejunostomy, inability to provide written consent, swallowing disorder, achalasia, Karnofsky Performance Status <80 and malnutrition are exclusion criteria. Patients will be randomised using online randomisation software. The intervention group (direct oral feeding) will receive a liquid oral diet for 2 weeks with gradually expanding daily maximums. The control group (delayed oral feeding) will receive enteral feeding via a jejunostomy during 5 days and then start the same liquid oral diet. The primary outcome measure is functional recovery. Secondary outcome measures are 30-day surgical complications; nutritional status; need for artificial nutrition; need for additional interventions; health-related quality of life. We aim to recruit 148 patients. Statistical analysis will be performed according to an intention to treat principle. Results are presented as risk ratios with corresponding 95% CIs. A two-tailed p<0.05 is considered statistically significant. Ethics and dissemination Our study protocol has received ethical approval from the Medical research Ethics Committees United (MEC-U). This study is conducted according to the principles of Good Clinical Practice. Verbal and written informed consent is

  6. Antithrombotic properties of rafigrelide: a phase 1, open-label, non-randomised, single-sequence, crossover study.

    PubMed

    Balasubramaniam, K; Viswanathan, G; Dragone, J; Grose-Hodge, R; Martin, P; Troy, S; Preston, P; Zaman, A G

    2014-07-01

    Platelets play a central role in atherothrombotic events. We investigated the effect of a novel platelet-lowering agent, rafigrelide, on thrombus formation and characteristics. In this phase 1, open-label, non-randomised, single-sequence, crossover study, healthy male volunteers received rafigrelide for 14 days (Period 1). Following a ≥6-week washout period, they then received rafigrelide + acetylsalicylic acid (ASA) for 14 days (Period 2). Thrombus formation was assessed ex vivo using the Badimon perfusion chamber, and thrombus characteristics were assessed using thromboelastography. A total of 15 volunteers were enrolled in the study and were assigned to Panel A or Panel B, which had different schedules of assessments. In Panel A, after treatment with rafigrelide alone (Period 1), mean (± standard deviation) platelet count was reduced from 283 (± 17) × 10⁹/l at Day 1, to 125 (± 47) × 10⁹/l at Day 14 (n=6) and thrombus area reduced under high and low shear conditions. Reductions in thrombus area under high shear conditions correlated with reductions in platelet count (r²=0.11, p=0.022; n=12). Rafigrelide treatment prolonged clot formation time and reduced clot strength. The addition of ASA to rafigrelide (Period 2) had no additional effect on platelet count or thrombus area under high or low shear conditions. Similar results were seen in Panel B for all parameters. The most common adverse events (≥3 participants per period) were thrombocytopenia and headache. While confirming the platelet-lowering effects of rafigrelide, this early phase study also indicates that rafigrelide has antithrombotic properties under both high and low shear conditions. PMID:24553755

  7. Vitamin E treatment in patients with nonalcoholic steatohepatitis: A six-month, open-label study of sixteen patients

    PubMed Central

    Yakaryilmaz, Fahri; Guliter, Sefa; Ozenirler, Seren; Erdem, Ozlem; Akyol, Gulen

    2004-01-01

    Background Free radicals have a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Decreasing oxidative stress might have beneficial effects on the biochemical and histologic progression of this disease. Objective We aimed to determine the therapeutic effect of vitamin E, a potent antioxidant, on liver enzymes and histology in NASH. Methods This 6-month, open-label study was conducted at the Departments of Gastroenterology and Pathology, Gazi University School of Medicine (Ankara, Turkey). Patients aged 18 to 70 years with biopsy-proven NASH were included in the study. All patients received vitamin E 800 U/d in 2 divided doses, orally (capsules) for 6 months. Patients were not advised to change their exercise or dietary habits. Body mass index (BMI) was calculated at months 0 (baseline) and 6. Histologic scoring of steatosis, necroinflammatory grade, and fibrosis stage was performed at 0 and 6 months. Liver enzyme activities (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT]) were monitored monthly. Control biopsy specimens were obtained at the end of the treatment. All of the liver biopsies were read by a single pathologist (G.A.) who was blinded to the clinical, laboratory, and histopathologic data, as well as the sequence of liver biopsies. Assessments of compliance and tolerability of treatment were performed using a pill count and patient interview, respectively, at the end of each month. Results Sixteen patients (12 men, 4 women; mean [SD] age, 45.5 [6.9] years [range, 37–60 years]) were enrolled. All patients completed 6 months of treatment. Mean BMI did not change significantly from baseline. Significant improvements in mean (SD) serum liver enzyme activities were observed at 6 months compared with baseline (ALT: 38.6 [16.3] U/L vs 84.8 [22.1] U/L, respectively, P = 0.001; AST: 29.8 [15.4] U/L vs 46.0 [16.0] U/L, respectively, P = 0.001; ALP: 154.6 [64

  8. An open-label pilot study of pulsed electromagnetic field therapy in the treatment of failed back surgery syndrome pain

    PubMed Central

    Harper, Wayne L; Schmidt, William K; Kubat, Nicole J; Isenberg, Richard A

    2015-01-01

    Persistent pain following back surgery remains a major treatment challenge. The primary objective of this open-label exploratory study was to investigate the analgesic effectiveness of pulsed electromagnetic field therapy administered twice daily over a 45-day period in 34 subjects (68% female) with persistent or recurrent pain following back surgery. A secondary goal was to guide the design of future randomized controlled trials that could target responsive subpopulations. All predefined primary and secondary outcomes, including change in pain intensity (PI), physical function (Oswestry Disability Index), analgesic consumption, and overall well-being (Patient Global Impression of Change), are reported. A responder analysis (≥30% reduction in PI versus baseline) was added as a post hoc evaluation. Safety outcomes, as well as results of a cost-avoidance survey, are also summarized. Of the 30 per-protocol subjects who completed the study, 33% reported a clinically meaningful (≥30%) reduction in PI. A higher response rate (60%) was reported for subjects who had undergone discectomy prior to the trial compared to subjects who had undergone other types of surgical interventions (decompression or fusion) without discectomy. Improvements in PI were paralleled by improvements in secondary outcomes. Relative to baseline, responders reported an average 44% and 55% reduction in back PI and leg PI (respectively), and an average 13% improvement in Oswestry Disability Index scores. In the per-protocol population, 50% of responders and 12% of nonresponders reported less analgesia consumption at the end of treatment versus baseline. Sixty-seven percent of per-protocol responders and 0% of nonresponders reported clinically meaningful improvement in overall well-being on the Patient Global Impression of Change scale. PMID:25678825

  9. An open-label pilot study of pulsed electromagnetic field therapy in the treatment of failed back surgery syndrome pain.

    PubMed

    Harper, Wayne L; Schmidt, William K; Kubat, Nicole J; Isenberg, Richard A

    2015-01-01

    Persistent pain following back surgery remains a major treatment challenge. The primary objective of this open-label exploratory study was to investigate the analgesic effectiveness of pulsed electromagnetic field therapy administered twice daily over a 45-day period in 34 subjects (68% female) with persistent or recurrent pain following back surgery. A secondary goal was to guide the design of future randomized controlled trials that could target responsive subpopulations. All predefined primary and secondary outcomes, including change in pain intensity (PI), physical function (Oswestry Disability Index), analgesic consumption, and overall well-being (Patient Global Impression of Change), are reported. A responder analysis (≥30% reduction in PI versus baseline) was added as a post hoc evaluation. Safety outcomes, as well as results of a cost-avoidance survey, are also summarized. Of the 30 per-protocol subjects who completed the study, 33% reported a clinically meaningful (≥30%) reduction in PI. A higher response rate (60%) was reported for subjects who had undergone discectomy prior to the trial compared to subjects who had undergone other types of surgical interventions (decompression or fusion) without discectomy. Improvements in PI were paralleled by improvements in secondary outcomes. Relative to baseline, responders reported an average 44% and 55% reduction in back PI and leg PI (respectively), and an average 13% improvement in Oswestry Disability Index scores. In the per-protocol population, 50% of responders and 12% of nonresponders reported less analgesia consumption at the end of treatment versus baseline. Sixty-seven percent of per-protocol responders and 0% of nonresponders reported clinically meaningful improvement in overall well-being on the Patient Global Impression of Change scale.

  10. Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer

    PubMed Central

    Dalgleish, Angus G; Stebbing, Justin; Adamson, Douglas JA; Arif, Seema Safia; Bidoli, Paolo; Chang, David; Cheeseman, Sue; Diaz-Beveridge, Robert; Fernandez-Martos, Carlos; Glynne-Jones, Rob; Granetto, Cristina; Massuti, Bartomeu; McAdam, Karen; McDermott, Raymond; Martín, Andrés J Muñoz; Papamichael, Demetris; Pazo-Cid, Roberto; Vieitez, Jose M; Zaniboni, Alberto; Carroll, Kevin J; Wagle, Shama; Gaya, Andrew; Mudan, Satvinder S

    2016-01-01

    Background: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. Methods: Patients were randomised (2 : 1) to IMM-101 (10 mg ml−l intradermally)+GEM (1000 mg m−2 intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. Results: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44–1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33–0.87, P=0.01). Conclusions: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study. PMID:27599039

  11. Safety and efficacy of polycalcium for improving biomarkers of bone metabolism: a 4-week open-label clinical study.

    PubMed

    Choi, Jae-Suk; Park, Mi-Yeon; Kim, Jong-Dae; Cho, Hyung Rae; Choi, In Soon; Kim, Joo-Wan

    2013-03-01

    Polycalcium is a mixture of Polycan and calcium lactate-gluconate 1:9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies. These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety. In total, 30 healthy women (range 40-60 years) were administered 400 mg of Polycalcium for 4 weeks. The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium. After 4 weeks of Polycalcium administration, 27 subjects completed the test plan. Three subjects withdrew their consent to participate. The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by -28.44%, 14.37%, 6.11%, and 1.42%, respectively. Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by -13.40%, 6.67%, -5.13%, -22.43%, and -3.04%, respectively. Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400  mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe. Polycalcium was apparently safe and efficacious.

  12. Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

    PubMed Central

    Lemoine, Patrick; Garfinkel, Doron; Laudon, Moshe; Nir, Tali; Zisapel, Nava

    2011-01-01

    Background Prolonged-release melatonin (PRM) 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation. Objective To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment. Methods Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary), adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]). Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM. Results Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as “good” or “very good” was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production. Conclusion Results support the efficacy and safety of PRM in primary insomnia patients aged 20–80 throughout 6–12 months of continuous therapy. PRM discontinuation even after 12 months was not associated with adverse events, withdrawal symptoms, or suppression of endogenous melatonin production. PMID:21845053

  13. Eldecalcitol improves muscle strength and dynamic balance in postmenopausal women with osteoporosis: an open-label randomized controlled study.

    PubMed

    Saito, Kimio; Miyakoshi, Naohisa; Matsunaga, Toshiki; Hongo, Michio; Kasukawa, Yuji; Shimada, Yoichi

    2016-09-01

    The antifracture efficacy of vitamin D in osteoporosis is due to its direct action on bones and indirect extraskeletal effects to prevent falls. Eldecalcitol is an analog of active vitamin D3 that improves bone mineral density and reduces the risk of osteoporotic fractures. However, the effects of eldecalcitol on muscle strength and static and dynamic postural balance are unclear. In this open-label randomized controlled study, we assessed the effects of eldecalcitol on muscle strength and static and dynamic postural balance in 50 postmenopausal women (mean age 74 years) with osteoporosis treated with bisphosphonate. Participants were randomly divided into a bisphosphonate group (alendronate at 35 mg/week; n = 25) or an eldecalcitol group (eldecalcitol at 0.75 μg/day and alendronate at 35 mg/week; n = 25) and were followed up for 6 months. Trunk muscle strength, including back extensor strength and iliopsoas muscle strength, was measured. Static standing balance was evaluated and the one leg standing test was performed to assess static postural balance. Dynamic sitting balance was evaluated and the 10-m walk test, functional reach test, and timed up and go test were performed to assess dynamic postural balance. At 6 months, there were no significant changes in any measure of muscle strength or balance in the bisphosphonate group, whereas eldecalcitol significantly increased back extensor strength (p = 0.012) and iliopsoas muscle strength (p = 0.035). Eldecalcitol also significantly improved findings on the timed up and go test (p = 0.001) and dynamic sitting balance (p = 0.015) at 6 months. These results with eldecalcitol may have an impact on prevention of falls.

  14. Safety, Tolerability, and Efficacy of Quetiapine in Youth with Schizophrenia or Bipolar I Disorder: A 26-Week, Open-Label, Continuation Study

    PubMed Central

    Pathak, Sanjeev; Earley, Willie R.; Liu, Sherry; DelBello, Melissa

    2013-01-01

    Abstract Objective The purpose of this study was to describe the safety, tolerability, and efficacy of quetiapine monotherapy continued for up to 26-weeks in youth with schizophrenia or bipolar I disorder. Methods Medically healthy boys and girls with a baseline Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) diagnosis of schizophrenia (ages 13–17 years) or a manic episode of bipolar I disorder (ages 10–17 years) who participated in one of two acute, double-blind, placebo-controlled studies of immediate-release quetiapine were potentially eligible to enroll in a 26-week, open-label study. During the open-label study, quetiapine was flexibly dosed at 400–800 mg/day, with options to reduce dosing to 200 mg/day based on tolerability. Safety and tolerability outcomes assessed from open-label baseline to week 26 included adverse events (AEs), metabolic/laboratory parameters, extrapyramidal symptoms, suicidality, and vital signs. Results Of 381 patients enrolled in the open-label study (n=176, schizophrenia; n=205, bipolar disorder diagnosis), 237 patients (62.2%) completed the 26-week study period (71.0%, schizophrenia; 54.6%, bipolar disorder). The most common AEs reported during the study included somnolence, headache, sedation, weight increase, and vomiting. A total of 14.9% of patients experienced a shift to potentially clinically significant low levels of high-density lipoprotein cholesterol and 10.2% of patients experienced a shift to potentially clinically significant high triglyceride levels. Weight gain ≥7% was reported in 35.6% of patients between open-label baseline and final visit. After adjustment for normal growth, 18.3% of study participants experienced clinically significant weight gain (i.e., increase in body mass index ≥0.5 standard deviations from baseline). Conclusions In this 26-week study, quetiapine flexibly dosed at 400–800 mg/day, with options to reduce dosing based on tolerability, was generally safe

  15. A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis

    PubMed Central

    Myers, Stephen P; O’Connor, Joan; Fitton, J Helen; Brooks, Lyndon; Rolfe, Margaret; Connellan, Paul; Wohlmuth, Hans; Cheras, Phil A; Morris, Carol

    2010-01-01

    Background: Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects. Purpose: This present study tested a Maritech® extract formulation, containing a blend of extracts from three different species of brown algae, plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee. Patients and methods: Participants (n = 12, five females [mean age, 62 ± 11.06 years] and seven males [mean age, 57.14 ± 9.20 years]) with a confirmed diagnosis of osteoarthritis of the knee were randomized to either 100 mg (n = 5) or 1000 mg (n = 7) of a Maritech® extract formulation per day. The formulation contained Maritech® seaweed extract containing Fucus vesiculosis (85% w/w), Macrocystis pyrifera (10% w/w) and Laminaria japonica (5% w/w) plus vitamin B6, zinc and manganese. Primary outcome was the average comprehensive arthritis test (COAT) score which is comprised of four sub-scales: pain, stiffness, difficulty with physical activity and overall symptom severity measured weekly. Safety measures included full blood count, serum lipids, liver function tests, urea, creatinine and electrolytes determined at baseline and week 12. All adverse events were recorded. Results: Eleven participants completed 12 weeks and one completed 10 weeks of the study. Using a multilevel linear model, the average COAT score was reduced by 18% for the 100 mg treatment and 52% for the 1000 mg dose at the end of the study. There was a clear dose response effect seen between the two treatments (P ≤ 0.0005) on the average COAT score and each of the four COAT subscales (pain, stiffness, difficulty with physical activity and overall symptom severity) (P ≤ 0.05). The preparation was well tolerated and the few adverse events were unlikely to be related to the study medication. There were no changes in blood parameters measured over the course of the study with the exception of

  16. The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids: results from an open-label comparative study.

    PubMed

    Mühlbacher, Ferdinand; Neumayer, Hans-Helmut; del Castillo, Domingo; Stefoni, Sergio; Zygmunt, Anthony J; Budde, Klemens

    2014-02-01

    This study evaluated the safety and efficacy of a sirolimus, corticosteroid, and cyclosporine reduction regimen in an open-label, 12-month trial of 420 de novo renal allograft recipients at 49 European transplant centers. One month post-transplantation, 357 patients were randomized to receive standard-dose cyclosporine (sCsA, n = 179) or reduced-dose cyclosporine (rCsA, n = 178). All patients also received sirolimus and corticosteroids. The primary end points were the rate of biopsy-confirmed acute rejection (BCAR) and renal function, as measured by serum creatinine. Baseline demographic and donor characteristics were similar between groups. BCAR rates at 12 months were not significantly different: 11.2% for rCsA patients and 16.2% for sCsA patients. Mean serum creatinine (±SEM) was significantly lower (1.75 ± 0.10 vs. 1.97 ± 0.07 mg/dl, P < 0.001), and creatinine clearance (±SEM; Nankivell method) was significantly higher (57.8 ± 1.78 vs. 49.5 ± 2.46 ml/min, P < 0.001) in patients receiving rCsA versus sCsA at 1 year, respectively. Patient and graft survival exceeded 98% in both groups. No significant differences in infection or malignancy were noted between groups. The rCsA with sirolimus and corticosteroid regimen resulted in excellent 12-month patient and graft survival, a low incidence of BCAR, and improved renal function in renal allograft recipients. Sirolimus administered with rCsA and corticosteroids provided adequate immunosuppression while reducing the potential for the nephrotoxic effects of cyclosporine. These findings may help to improve long-term renal allograft outcomes.

  17. Efficacy and safety of telbivudine treatment: an open-label, prospective study in pregnant women for the prevention of perinatal transmission of hepatitis B virus infection.

    PubMed

    Han, G-R; Jiang, H-X; Yue, X; Ding, Y; Wang, C-M; Wang, G-J; Yang, Y-F

    2015-09-01

    We evaluated the efficacy and safety of telbivudine (LdT, 600 mg/day) vs control patients (no treatment) in decreasing vertical transmission of HBV, in HBeAg-positive mothers (HBVDNA >6log(10) copies/mL). HBeAg-positive pregnant women either in the second or third trimester were recruited in a prospective, case-control, open-label study, at the Second Affiliated Hospital of the Southeast University, China (February 2008-December 2010). Efficacy (month 7: HBVDNA (+), HBsAg (+) infants) in either the overall group or the treated group and control group was analysed using student's t-test. Infants were followed for at least 1 year. 362 women received LdT (second trimester n = 257; third trimester n = 105) and 92 were untreated. Before delivery, the mean maternal HBVDNA was 2.73, 2.47, 3.34 and 7.94 log10 copies/mL in the overall, second and third trimester treated and control groups, respectively (P < 0.001). At birth, 11.8% of babies overall (43/365), 13.5% (35/259) of those treated in the second trimester, 7.5% of those treated in the third trimester (8/106) and 20.7% (19/92) of untreated infants were HBsAg positive. At month 7, none of the LdT-treated infant had detectable HBVDNA, while eight infants from control mothers were HBsAg positive. Vertical transmission was 0% in LdT treated and 9.3% (8/86) in the control groups (P < 0.001). No difference in the vertical transmission rate was found in mothers treated in the second or third trimester. LdT treatment was safe for mothers and infants, and no congenital deformities were reported.

  18. Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.

    PubMed

    Komatsu, Yoshito; Okita, Kenji; Yuki, Satoshi; Furuhata, Tomohisa; Fukushima, Hiraku; Masuko, Hiroyuki; Kawamoto, Yasuyuki; Isobe, Hiroshi; Miyagishima, Takuto; Sasaki, Kazuaki; Nakamura, Michio; Ohsaki, Yoshinobu; Nakajima, Junta; Tateyama, Miki; Eto, Kazunori; Minami, Shinya; Yokoyama, Ryoji; Iwanaga, Ichiro; Shibuya, Hitoshi; Kudo, Mineo; Oba, Koji; Takahashi, Yasuo

    2015-07-01

    The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.

  19. Palonosetron versus ondansetron as rescue medication for postoperative nausea and vomiting: a randomized, multicenter, open-label study

    PubMed Central

    2014-01-01

    Background This study compared palonosetron and ondansetron as rescue medications for postoperative nausea and vomiting (PONV) in patients who received prophylactic ondansetron. Although guidelines recommend use of an agent from a different class when prophylaxis has failed, palonosetron has unique properties relative to other serotonin 5-HT3 receptor antagonists. Prior trials assessing its use for rescue have had conflicting results. Although palonosetron has compared favorably with ondansetron for PONV prevention, the drugs have not been compared in the rescue setting of failure of 5-HT3 receptor antagonist prophylaxis. Methods This was a randomized, open-label, multicenter trial comparing the efficacy and safety of intravenous palonosetron 0.075 mg and intravenous ondansetron 4 mg in patients experiencing PONV following laparoscopic abdominal or gynecological surgery despite prophylactic ondansetron. Results Of 239 patients screened, 220 were enrolled and 98 were treated for PONV: 48 and 50 in the palonosetron and ondansetron arms, respectively. Complete control during 72 hours after study drug administration was achieved in 25.0% of palonosetron recipients and 18.0% of ondansetron recipients (95% confidence interval [CI], -9.2, 23.3; p = 0.40). Corresponding incidences of vomiting were 29.2% for palonosetron and 48.0% for ondansetron (95% CI, -0.06, 37.7; p = 0.057), and 62.5% and 56.0% required additional rescue treatment, respectively (95% CI, -25.9, 12.9; p = 0.52). Other than a similar incidence of procedural pain in the 2 groups, the most common treatment-emergent adverse events, which were generally mild, were headache (14.6% vs 12.0%), constipation (8.3% vs 10.0%), and dizziness (6.3% vs 8.0%), for the palonosetron and ondansetron groups, respectively. Conclusions Palonosetron and ondansetron did not show differences in the primary efficacy endpoint of CC during the 72 hours after study drug administration. There was a trend toward less

  20. Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma with Drug Eluting Beads: Results of an Open-Label Study of 62 Patients

    SciTech Connect

    Malagari, Katerina Chatzimichael, Katerina; Alexopoulou, Efthymia; Kelekis, Alexios; Hall, Brenda; Dourakis, Spyridon; Delis, Spyridon; Gouliamos, Athanasios; Kelekis, Dimitrios

    2008-03-15

    The purpose of this study was to assess the safety and efficacy of doxorubicin-loaded beads (DC Beads) delivered by transarterial embolization for the treatment of unresectable hepatocellular carcinoma (HCC). This open-label, single-center, single-arm study included 62 cirrhotic patients with documented single unresectable HCC. Mean tumor diameter was 5.6 cm (range, 3-9 cm) classified as Okuda stages 1 (n = 53) and 2 (n = 9). Patients received repeat embolizations with doxorubicin-loaded beads every 3 months (maximum of three). The maximum doxorubicin dose was 150 mg per embolization, loaded in DC Beads of 100-300 or 300-500 {mu}m. Regarding efficacy, overall, an objective response according to the European Association for the Study of the Liver criteria was observed in 59.6%, 81.8%, and 70.8% across three treatments. A complete response was observed in 4.8% after the first procedure and 3.6% and 8.3% after the second and third procedures, respectively. At 9 months a complete response was seen in 12.2%, an objective response in 80.7%, progressive disease in 6.8%, and 12.2% showed stable disease. Mean tumor necrosis ranged from 77.4% to 83.9% (range, 28.6%-100%) across three treatments. {alpha}-Fetoprotein levels showed a mean decrease of 1123 ng/ml (95% CI = 846-1399; p = 3 x 10{sup -11}) after the first session and remained stable after the second and third embolizations (42 and 70 ng/ml decrease, respectively). Regarding safety, bilirubin, {gamma}-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase showed only transient increases during the study period. Severe procedure-related complications were seen in 3.2% (cholecystitis, n 1; liver abscess, n = 1). Postembolization syndrome was observed in all patients. We conclude that hemoembolization using doxorubicin-loaded DC Beads is a safe and effective treatment of HCC as demonstrated by the low complication rate, increased tumor response, and sustained reduction of

  1. Orally Formulated Artemisinin in Healthy Fasting Vietnamese Male Subjects: A Randomized, Four-Sequence, Open-Label, Pharmacokinetic Crossover Study

    PubMed Central

    Hien, Tran Tinh; Hanpithakpong, Warunee; Truong, Nguyen Thanh; Dung, Nguyen Thi; Toi, Pham Van; Farrar, Jeremy; Lindegardh, Niklas; Tarning, Joel; Ashton, Michael

    2011-01-01

    Background Artemisinin derivatives are used in antimalarial drug combination therapy. Artemisinin and piperaquine have recently been proven to be prospective candidates for combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria. Objective The goal of this study was to evaluate the relative bioavailability and to characterize the pharmacokinetic properties of a new micronized powder formulation of artemisinin against the previous standard Vietnamese formulation when administered as a single oral dose or in combination with piperaquine. Methods This was a single-center, randomized, 4-sequence, open-label, crossover study conducted in 15 healthy male Vietnamese volunteers under fasting conditions with a washout period of 3 weeks between study visits. A single oral dose of 160 or 500 mg of artemisinin was administered alone or in combination with piperaquine. Potential adverse events were monitored daily by the clinician and by using laboratory test results. Frequent blood samples were drawn for 12 hours after dose. Artemisinin was quantified in plasma using LC-MS/MS. Pharmacokinetic parameters were computed from the plasma concentration–time profiles using a noncompartmental analysis method. Results Pharmacokinetic parameters Tmax, Cmax, AUC0-∞, Vd/F, CL/F, and t1/2 (mean [SD]) for the new formulation of artemisinin were 1.83 (0.88) hours, 178 (97) ng/mL, 504 (210) h × ng/mL, 1270 (780) L, 401 (260) L/h, and 2.21 (0.29) hours, respectively. The mean percentage of the test/reference formulation ratio for the logarithmically transformed values of Cmax, AUC0–last, and AUC0–∞ were 121% (90% CI, 92.5–158), 122% (90% CI, 101–148), and 120% (90% CI, 98.0–146), respectively. Conclusions This single-dose study found that the dose-normalized Cmax, AUC0–last, and AUC0–∞ mean geometric differences between the test and reference formulations were relatively small (<40%) and will probably not have a clinical impact in the

  2. The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study

    PubMed Central

    Hosomi, Naohisa; Nagai, Yoji; Kohriyama, Tatsuo; Ohtsuki, Toshiho; Aoki, Shiro; Nezu, Tomohisa; Maruyama, Hirofumi; Sunami, Norio; Yokota, Chiaki; Kitagawa, Kazuo; Terayama, Yasuo; Takagi, Makoto; Ibayashi, Setsuro; Nakamura, Masakazu; Origasa, Hideki; Fukushima, Masanori; Mori, Etsuro; Minematsu, Kazuo; Uchiyama, Shinichiro; Shinohara, Yukito; Yamaguchi, Takenori; Matsumoto, Masayasu

    2015-01-01

    Background Although statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients. Methods This is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints. Finding Although 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events. Interpretation Although whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis. Funding This study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and

  3. Rotigotine transdermal system for long-term treatment of patients with advanced Parkinson's disease: results of two open-label extension studies, CLEOPATRA-PD and PREFER.

    PubMed

    LeWitt, Peter A; Boroojerdi, Babak; Surmann, Erwin; Poewe, Werner

    2013-07-01

    Open-label extensions [studies SP516 (NCT00501969) and SP715 (NCT00594386)] of the CLEOPATRA-PD and PREFER studies were conducted to evaluate the safety, tolerability and efficacy of the dopaminergic agonist, rotigotine, over several years of follow-up in patients with advanced Parkinson's disease (PD). Eligible subjects completing the double-blind trials received open-label adjunctive rotigotine (≤16 mg/24 h) for up to 4 and 6 years in Studies SP516 and SP715, respectively. Safety and tolerability were assessed using adverse events, vital signs and laboratory parameters, and efficacy assessed using the unified Parkinson's disease rating scale (UPDRS). Of the 395 and 258 patients enrolled in the SP516 and SP715 studies, 48 and 45 % completed, respectively. Adverse events were typically dopaminergic effects [e.g., somnolence (18-25 %/patient-year), insomnia (5-7 %/patient-year), dyskinesias (4-8 %/patient-year) and hallucinations (4-8 %/patient-year)], or related to the transdermal application of a patch (application site reactions: 14-15 %/patient-year). There were no clinically relevant changes in vital signs or laboratory parameters in either study. Mean UPDRS part II (activities of daily living) and part III (motor function) total scores improved from double-blind baseline during dose titration, then gradually declined over the maintenance period. In study SP516, mean UPDRS part II and III total scores were 0.8 points above and 2.8 points below double-blind baseline, respectively, at end of treatment. In study SP715, mean UPDRS part II and III total scores were 4.1 points above and 0.2 points below baseline, respectively, at end of treatment. In these open-label studies, adjunctive rotigotine was efficacious with an acceptable safety and tolerability profile in patients with advanced PD for up to 6 years.

  4. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

    PubMed Central

    2013-01-01

    Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). Results Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures

  5. Subgroup Analyses from a Phase 3, Open-Label, Randomized Study of Eribulin Mesylate Versus Capecitabine in Pretreated Patients with Advanced or Metastatic Breast Cancer

    PubMed Central

    Twelves, Chris; Awada, Ahmad; Cortes, Javier; Yelle, Louise; Velikova, Galina; Olivo, Martin S.; Song, James; Dutcus, Corina E.; Kaufman, Peter A.

    2016-01-01

    PURPOSE AND METHODS Our secondary analyses compared survival with eribulin versus capecitabine in various patient subgroups from a phase 3, open-label, randomized study. Eligible women aged ≥18 years with advanced/metastatic breast cancer and ≤3 prior chemotherapies (≤2 for advanced/metastatic disease), including an anthracycline and taxane, were randomized 1:1 to intravenous eribulin mesylate 1.4 mg/m2 on days 1 and 8 or twice-daily oral capecitabine 1250 mg/m2 on days 1–14 (21-day cycles). RESULTS In the intent-to-treat population (eribulin 554 and capecitabine 548), overall survival appeared longer with eribulin than capecitabine in various subgroups, including patients with human epidermal growth factor receptor 2-negative (15.9 versus 13.5 months, respectively), estrogen receptor-negative (14.4 versus 10.5 months, respectively), and triple-negative (14.4 versus 9.4 months, respectively) disease. Progression-free survival was similar between the treatment arms. CONCLUSIONS Patients with advanced/metastatic breast cancer and human epidermal growth factor receptor 2-, estrogen receptor-, or triple-negative disease may gain particular benefit from eribulin as first-, second-, and third-line chemotherapies. TRIAL REGISTRATION (PRIMARY STUDY) This study reports the subgroup analyses of eribulin versus capecitabine from a phase 3, open-label, randomized study (www.clinicaltrials.gov; ClinicalTrials.gov identifier: NCT00337103). PMID:27398025

  6. Self-reported Recent PrEP Dosing and Drug Detection in an Open Label PrEP Study.

    PubMed

    Amico, K Rivet; Mehrotra, Megha; Avelino-Silva, Vivian I; McMahan, Vanessa; Veloso, Valdilea G; Anderson, Peter; Guanira, Juan; Grant, Robert

    2016-07-01

    Monitoring adherence to pre-exposure prophylaxis (PrEP) is part of the recommended package for PrEP prescribing, yet ongoing concerns about how to do so confidently are exacerbated by gross discrepancies in reported and actual use in clinical trials. We evaluated concordance between reports of recent PrEP dosing collected via neutral interviewing and drug quantitation in the iPrEx open-label extension, where participants (n = 1172) had the choice to receive or not receive PrEP. Self-report of recent dosing (at least one PrEP dose in the past 3-day) was the most common report (84 % of participants), and among these 83 % did have quantifiable levels of drug. The vast majority of those reporting no doses in the past 3-day (16 % of the sample) did not have quantifiable levels of drug (82 %). Predictors of over-report of dosing included younger age and lower educational attainment. Monitoring recent PrEP use through neutral interviewing may be a productive approach for clinicians to consider in implementation of real-world PrEP. Strategies to capture longer term or prevention-effective PrEP use, particularly for younger cohorts, are needed.

  7. Long-Term, Open-Label, Safety Study of Edivoxetine 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment.

    PubMed

    Ball, Susan G; Atkinson, Sarah; Sparks, JonDavid; Bangs, Mark; Goldberger, Celine; Dubé, Sanjay

    2015-06-01

    Long-term safety, tolerability, and efficacy of adjunctive edivoxetine hydrochloride (hereafter edivoxetine), a highly selective and potent norepinephrine reuptake inhibitor, was assessed in patients with major depressive disorder (MDD) experiencing partial response to selective serotonin reuptake inhibitor treatment. Data are from a multicenter, 54-week, open-label trial of adjunctive edivoxetine 12 to 18 mg once daily in patients with MDD who had experienced partial response by history to 6 or more weeks of current selective serotonin reuptake inhibitor therapy and who had a 17-item GRID Hamilton Rating Scale for Depression total score 16 or higher at study entry. Safety measures included discontinuation rate, treatment-emergent adverse events, serious adverse events, and vital signs. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale. Of 608 patients, 328 (54%) completed the open-label adjunctive treatment. Study discontinuation due to adverse events occurred in 17.0%, and there were 13 serious adverse events (1 death). Treatment-emergent adverse events 5% or higher were nausea, hyperhidrosis, constipation, headache, dry mouth, dizziness, vomiting, insomnia, and upper respiratory tract infection. Mean increases were observed in systolic blood pressure (range, 0.0-2.3 mm Hg), diastolic blood pressure (range, 1.9-3.3 mm Hg), and pulse (range, 5.9-8.4 beats per minute). Mean improvements on the Montgomery-Åsberg Depression Rating Scale (-17.0) were observed from baseline to week 54. The safety profile from this study provides an overview of outcomes associated with edivoxetine and norepinephrine reuptake inhibition as an adjunctive treatment in patients with MDD who were treated up to 1 year. PMID:25815754

  8. Maintenance of Cognitive Performance and Mood for Individuals with Alzheimer's Disease Following Consumption of a Nutraceutical Formulation: A One-Year, Open-Label Study.

    PubMed

    Remington, Ruth; Bechtel, Cynthia; Larsen, David; Samar, Annemarie; Page, Robert; Morrell, Christopher; Shea, Thomas B

    2016-01-01

    Nutritional interventions have shown varied efficacy on cognitive performance during Alzheimer's disease (AD). Twenty-four individuals diagnosed with AD received a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) under open-label conditions (ClinicalTrials.gov NCT01320527). Primary outcome was cognitive performance. Secondary outcomes were behavioral and psychological symptoms of dementia (BPSD) and activities of daily living. Participants maintained their baseline cognitive performance and BPSD over 12 months. These findings are consistent with improvement in cognitive performance and BPSD in prior placebo-controlled studies with NF, and contrast with the routine decline for participants receiving placebo.

  9. Aripiprazole once-monthly 400 mg for long-term maintenance treatment of schizophrenia: a 52-week open-label study

    PubMed Central

    Peters-Strickland, Timothy; Baker, Ross A; McQuade, Robert D; Jin, Na; Eramo, Anna; Perry, Pamela; Johnson, Brian R; Duca, Anna; Sanchez, Raymond

    2015-01-01

    Background: Long-term maintenance treatment with an antipsychotic is often required to prevent relapse and mitigate functional deterioration in patients with schizophrenia. Aims: This study assessed the long-term safety, tolerability, and maintenance of the therapeutic effect of aripiprazole once-monthly 400 mg (AOM 400) in patients with schizophrenia. Methods: This 52-week, open-label study included patients previously enrolled in 1 of 2 AOM 400 randomized controlled trials (RCTs) and de novo patients. Safety endpoints included adverse events (AEs), suicidality, extrapyramidal symptoms, injection-site pain, and clinically relevant changes in clinical and laboratory values. The primary efficacy endpoint was the percentage of stable patients at baseline who remained stable at the last visit of the AOM 400 maintenance phase. All endpoints were assessed with descriptive statistics; there were no formal planned statistical analyses. Results: Of 1,247 patients screened, 1,178 enrolled in the study (194 de novo and 984 patients from the RCTs) and 1,081 received maintenance treatment with AOM 400. The maintenance phase completion rate was 79.4% at 52 weeks. Treatment-emergent AEs in ⩾5% of patients during open-label AOM 400 treatment were headache (7.6%), nasopharyngitis (7.0%), anxiety (6.8%), and insomnia (6.6%). There were no clinically relevant changes in safety parameters of interest. Ninety-five percent of stable patients at baseline remained stable at their last visit during the AOM 400 maintenance phase. Conclusions: The long-term safety and tolerability profile of AOM 400 was comparable to the RCTs, and the long-term therapeutic effect was maintained. PMID:27336044

  10. Evaluation of safety and efficacy of zonisamide in adult patients with partial, generalized, and combined seizures: an open labeled, noncomparative, observational Indian study

    PubMed Central

    Dash, Amitabh; Ravat, Sangeeta; Srinivasan, Avathvadi Venkatesan; Shetty, Ashutosh; Kumar, Vivek; Achtani, Renu; Mathur, Vivek Narain; Maramattom, Boby Varkey; Bajpai, Veeresh; Manjunath, Nanjappa C; Narayana, Randhi Venkata; Mehta, Suyog

    2016-01-01

    A prospective, multicentric, noncomparative open-label observational study was conducted to evaluate the safety and efficacy zonisamide in Indian adult patients for the treatment of partial, generalized, or combined seizures. A total of 655 adult patients with partial, generalized, or combined seizures from 30 centers across India were recruited after initial screening. Patients received 100 mg zonisamide as initiating dose as monotherapy/adjunctive therapy for 24 weeks, with titration of 100 mg every 2 weeks if required. Adverse events, responder rates, and seizure freedom were observed every 4 weeks. Efficacy and safety were also assessed using Clinicians Global Assessment of Response to Therapy and Patients Global Assessment of Tolerability to Therapy, respectively. Follow-up was conducted for a period of 24 weeks after treatment initiation. A total of 655 patients were enrolled and received the treatment and 563 completed the evaluation phase. A total of 20.92% of patients received zonisamide as monotherapy or alternative monotherapy and 59.85% patients received zonisamide as first adjunctive therapy. Compared with baseline, 41.22% of patients achieved seizure freedom and 78.6% as responder rate at the end of 24 week study. Most commonly reported adverse events were loss of appetite, weight loss, sedation, and dizziness, but discontinuation due to adverse events of drug was seen in 0.92% of patients. This open label real-world study suggests that zonisamide is an effective and well-tolerated antiepileptic drug in Indian adults for treatment of partial, generalized as well as combined seizures type. No new safety signals were observed. PMID:27013882

  11. Adjunctive Triple Chronotherapy (Combined Total Sleep Deprivation, Sleep Phase Advance, and Bright Light Therapy) Rapidly Improves Mood and Suicidality in Suicidal Depressed Inpatients: An Open Label Pilot Study

    PubMed Central

    Sahlem, Gregory L.; Kalivas, Benjamin; Fox, James B.; Lamb, Kayla; Roper, Amanda; Williams, Emily N.; Williams, Nolan R.; Korte, Jeffrey E.; Zuschlag, Zachary D.; El Sabbagh, Salim; Guille, Constance; Barth, Kelly S.; Uhde, Thomas W.; George, Mark S.; Short, E.Baron

    2014-01-01

    Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N=10, Mean age=44±16.4SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33–36 hours), followed by a three-night sleep phase advance along with four 30-minute sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7±4.2SD at baseline to a mean of 9.4±7.3SD on day five (p=.002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5±8.5SD at baseline to a mean of 7.2±5.5SD on day five (p=.01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed. PMID:25231629

  12. Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study.

    PubMed

    Sahlem, Gregory L; Kalivas, Benjamin; Fox, James B; Lamb, Kayla; Roper, Amanda; Williams, Emily N; Williams, Nolan R; Korte, Jeffrey E; Zuschlag, Zachary D; El Sabbagh, Salim; Guille, Constance; Barth, Kelly S; Uhde, Thomas W; George, Mark S; Short, E Baron

    2014-12-01

    Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N = 10, Mean age = 44 ± 16.4 SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33-36 h), followed by a three-night sleep phase advance along with four 30-min sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7 ± 4.2 SD at baseline to a mean of 9.4 ± 7.3 SD on day five (p = .002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5 ± 8.5 SD at baseline to a mean of 7.2 ± 5.5 SD on day five (p = .01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed.

  13. A Multicenter, Open-Label Trial to Evaluate the Quality of Life in Adults with ADHD Treated with Long-Acting Methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) Study

    ERIC Educational Resources Information Center

    Mattos, Paulo; Rodrigues Louza, Mario; Fernandes Palmini, Andre Luis; de Oliveira, Irismar Reis; Lopes Rocha, Fabio

    2013-01-01

    The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. Objective: To assess the effectiveness of Methyphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. Method: A 12-week, multicenter, open-label trial involving 60 patients was used. The…

  14. WIN OVER study: Efficacy and safety of olmesartan in Indian hypertensive patients: Results of an open label, non-comparative, multi-centric, post marketing observational study

    PubMed Central

    Kumbla, D.K.; Kumar, S.; Reddy, Y.V.; Trailokya, A.; Naik, M.

    2014-01-01

    Background Hypertension is a global health problem. Multiple classes of drugs including angiotensin receptor blockers (ARBs) are available for the treatment of hypertension. Olmesartan is a relatively newer ARB used in hypertension management. Objective To assess the efficacy and safety of WIN-BP (Olmesartan 20 mg/40 mg) tablet in Indian patients with hypertension. Material and methods An open label, non-comparative, multi-centric, real world post marketing observational study included Indian adult hypertensive patients who were treated with olmesartan 20 mg/40 mg tablet once daily for six months. The primary outcome was reduction of systolic blood pressure (SBP) to <140 mmHg and diastolic BP (DBP) to <90 mmHg at 3 and 6 months after initiation of treatment with olmesartan. All reported adverse events were recorded. Results A total of 8940 patients were enrolled in this study. Baseline SBP of 164 mmHg was reduced to 153, 145, 134 and 130 mmHg at the end of 15 days, 1, 3 and 6 months respectively. Similarly, baseline DBP of 100 mmHg was reduced to 93, 89, 84 and 82 mmHg at the end of 15 days, 1, 3 and 6 months respectively. The reduction in both systolic and diastolic blood pressure from day 15 to month 6 was statistically significant (p < 0.0001) with olmesartan treatment. The percentage of responders for both systolic and diastolic blood pressure increased consistently from day 15 to month 6. Only 0.08% patients reported the adverse events. No serious adverse event was reported in the study. Conclusion Olmesartan 20 mg/40 mg is effective and well tolerated without any serious adverse events in patients with hypertension. PMID:24973841

  15. An open-label, two-stage, phase II study of bevacizumab and lapatinib in children with recurrent or refractory ependymoma: a collaborative ependymoma research network study (CERN).

    PubMed

    DeWire, Mariko; Fouladi, Maryam; Turner, David C; Wetmore, Cynthia; Hawkins, Cynthia; Jacobs, Carmen; Yuan, Ying; Liu, Diane; Goldman, Stewart; Fisher, Paul; Rytting, Michael; Bouffet, Eric; Khakoo, Yasmin; Hwang, Eugene I; Foreman, Nicholas; Stewart, Clinton F; Gilbert, Mark R; Gilbertson, Richard; Gajjar, Amar

    2015-05-01

    Co-expression of ERBB2 and ERBB4, reported in 75% of pediatric ependymomas, correlates with worse overall survival. Lapatinib, a selective ERBB1 and ERBB2 inhibitor has produced prolonged disease stabilization in patients with ependymoma in a phase I study. Bevacizumab exposure in ependymoma xenografts leads to ablation of tumor self-renewing cells, arresting growth. Thus, we conducted an open-label, phase II study of bevacizumab and lapatinib in children with recurrent ependymomas. Patients ≤ 21 years of age with recurrent ependymoma received lapatinib orally twice daily (900 mg/m(2)/dose to the first 10 patients, and then 700 mg/m(2)/dose) and bevacizumab 10 mg/kg intravenously on days 1 and 15 of a 28-day course. Lapatinib serum trough levels were analyzed prior to each course. Total and phosphorylated VEGFR2 expression was measured in peripheral blood mononuclear cells (PBMCs) before doses 1 and 2 of bevacizumab and 24-48 h following dose 2 of bevacizumab. Twenty-four patients with a median age of 10 years (range 2-21 years) were enrolled; 22 were eligible and 20 evaluable for response. Thirteen had anaplastic ependymoma. There were no objective responses; 4 patients had stable disease for ≥ 4 courses (range 4-14). Grade 3 toxicities included rash, elevated ALT, and diarrhea. Grade 4 toxicities included peri-tracheostomy hemorrhage (n = 1) and elevated creatinine phosphokinase (n = 1). The median lapatinib pre-dose trough concentration was 3.72 µM. Although the combination of bevacizumab and lapatinib was well tolerated in children with recurrent ependymoma, it proved ineffective.

  16. The Beta-hCG + Erythropoietin in Acute Stroke (BETAS) study A three center, single dose, open label, non-controlled, Phase IIa safety trial

    PubMed Central

    Cramer, Steven C.; Fitzpatrick, Camille; Warren, Michael; Hill, Michael D.; Brown, David; Whitaker, Laura; Ryckborst, Karla J.; Plon, Lawrence

    2010-01-01

    Background Animal data suggest the utility beta-hCG followed by erythropoietin to promote brain repair after stroke. The current study directly translated these results by evaluating safety of this sequential growth factor therapy via a three center, single dose, open label, non-controlled, Phase IIa trial. Methods Patients with ischemic stroke 24–48 hours old and NIHSS score of 6–24 started a nine day course of beta-hCG (once-daily on days 1, 3 and 5 of study participation) followed by erythropoietin (once-daily on days 7, 8, and 9 of study participation). This study also evaluated performance of serially measured domain-specific endpoints. Results A total of 15 patients were enrolled. Two deaths occurred, neither related to study medications. No safety concerns were noted among clinical or laboratory measures, including screening for DVT and serial measures of serum hemoglobin. In several instances, domain-specific endpoints provided greater insight into impairments as compared to global outcome measures. Conclusions Results support the safety of this sequential, two growth factor therapy initiated 24–48 hours after stroke onset. PMID:20203320

  17. A multicenter, open-label extension study of velaglucerase alfa in Japanese patients with Gaucher disease: Results after a cumulative treatment period of 24months.

    PubMed

    Ida, Hiroyuki; Tanaka, Akemi; Matsubayashi, Tomoko; Murayama, Kei; Hongo, Teruaki; Lee, Hak-Myung; Mellgard, Björn

    2016-07-01

    Enzyme replacement therapy (ERT) with exogenous glucocerebrosidase is indicated to treat symptomatic Gaucher disease (GD), a rare, inherited metabolic disorder. ERT with velaglucerase alfa, which is produced in a human cell line using gene activation technology, was studied in a 12-month phase III trial in Japanese patients with type 1 or 3 GD who were switched from imiglucerase ERT (n=6); the current, open-label, 12-month extension study was designed to assess longer-term safety and efficacy. Two adult and three pediatric patients (aged <18years) were enrolled into the extension study. Every-other-week intravenous infusions were administered for 63-78weeks at average doses between 51.5 and 60.7units/kg. Three non-serious adverse events were considered related to velaglucerase alfa treatment, but no patient discontinued from the study. Six serious but non-drug-related adverse events were reported. No patient tested positive for anti-velaglucerase alfa antibodies. Hemoglobin concentrations, platelet counts, and liver and spleen volumes (normalized to body weight) in these patients were generally stable over a cumulative 24-month period from the baseline of the parent trial. The data suggest that velaglucerase alfa was well tolerated and maintained clinical stability in Japanese GD patients over 2years after switching from imiglucerase. ClinicalTrials.gov identifier NCT01842841. PMID:27241455

  18. Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study

    PubMed Central

    Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun

    2016-01-01

    Objective The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. Methods aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 2, 4, 8, and 12. Predictors for PANSS response (≥20% reduction) were investigated. Results The PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, p<0.001). Moreover, 51.0% of participants experienced a response at week 12. Premature discontinuation of blonanserin occurred in 17 patients (17.0%); 4 of these patients dropped out due to adverse events. The patients who benefited the most from blonanserin were those with severe symptoms despite a treatment with a higher dose of AAP. Conclusion Blonanserin augmentation could be an effective strategy for patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP. PMID:27482249

  19. Safety and tolerability of a body wash and moisturizer when applied to infants and toddlers with a history of atopic dermatitis: results from an open-label study.

    PubMed

    Simpson, Eric; Trookman, Nathan S; Rizer, Ronald L; Preston, Norman; Colón, Luz E; Johnson, Lori A; Gottschalk, Ronald W

    2012-01-01

    Improving skin barrier function and moisturizing without irritation are important components of managing patients with atopic dermatitis. This study evaluated the safety and tolerability of a body wash and moisturizer regimen for infants and toddlers with atopic dermatitis. This was an open-label study involving 56 children (3-36 months old) with a history of atopic dermatitis. The skin care regimen (Cetaphil Restoraderm Skin Restoring Body Wash and Cetaphil Restoraderm Skin Restoring Moisturizer; Galderma Laboratories, L.P.) was used at least once daily, but no more than twice daily, for 4 weeks. The primary variable of interest was the worst postbaseline scores for local tolerability (expressed as success or failure) using a 4-point scale for each component (erythema, edema, scaling and dryness, rash, and signs of discomfort upon application). Assessments of moisture content of the stratum corneum and transepidermal water loss were also performed. Fifty-three children completed the study. The percentage of subjects with no erythema increased from 33.9% to 50.0% by Week 4. The percentage of subjects with no scaling or dryness increased from 58.9% to 85.2% at Week 4. A statistically significant increase in corneometry from baseline (p < 0.001) and a statistically significant decrease in transepidermal water loss (p = .009) were observed. The body wash and moisturizer regimen was safe and well tolerated and improved hydration and skin barrier function in infants and toddlers as young as 3 months of age with a history of atopic dermatitis.

  20. The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

    PubMed

    Deuse, Tobias; Bara, Christoph; Barten, Markus J; Hirt, Stephan W; Doesch, Andreas O; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Garbade, Jens; Wimmer, Peter; May, Christoph; Porstner, Martina; Schulz, Uwe

    2015-11-01

    In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein.

  1. Combination treatment of fingolimod with antidepressants in relapsing–remitting multiple sclerosis patients with depression: a multicentre, open-label study – REGAIN

    PubMed Central

    Bayas, Antonios; Schuh, Katrin; Baier, Monika; Vormfelde, Stefan Viktor; Koppai-Reiner, Joachim

    2016-01-01

    Objectives: Approximately one in two patients with multiple sclerosis (MS) suffer from comorbid depression. The primary objective of this study was to evaluate the safety and tolerability of fingolimod and antidepressant combination in relapsing–remitting MS patients with mild-to-moderate depression. Efficacy outcome variables were quality of life (QoL), fatigue, disability and depression. Methods: Patients received open-label fingolimod 0.5 mg over 2 weeks, followed by fingolimod plus citalopram (40 mg), fluoxetine (40 mg) or venlafaxine (150 mg) over 16 weeks. The antidepressant was selected at the physician’s discretion. Results: In total, 54 patients were recruited at 25 centres across Germany. No new safety signals (including cardiac) emerged compared with previous clinical studies. Adverse events (mostly mild-to-moderate) were reported in 43 patients. A total of three patients had serious adverse events and 10 discontinued the study. QoL (mean [95% confidence interval]) improved by 2.2 (−3.3, −1.2; Patient Reported Indices for MS questionnaire), fatigue by 8.2 (−13.1, −3.3; modified Fatigue Impact Scale) and depression by 6.3 (−8.4, −4.2; Hamilton Depression Scale) points. However, the results must be interpreted cautiously owing to limited patient numbers. Conclusions: Combination of fingolimod with antidepressant medication showed no unexpected safety signals. Patient-reported outcomes (QoL, disability, fatigue and depression) remained stable or improved. PMID:27582893

  2. Efficacy and safety of flexibly dosed paliperidone palmitate in Chinese patients with acute schizophrenia: an open-label, single-arm, prospective, interventional study.

    PubMed

    Si, Tianmei; Zhang, Kerang; Tang, Jisheng; Fang, Maosheng; Li, Keqing; Zhuo, Jianmin; Feng, Yu

    2015-01-01

    This open-label, single-arm, multicenter, 13-week, prospective study explored the efficacy, safety, and tolerability of paliperidone palmitate (150 milligram equivalents [mg eq] [day 1], 100 mg eq [day 8], both deltoid injections; 75-150 mg eq, deltoid/gluteal injection) in Chinese patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score ≥70), who previously had unsatisfactory therapeutic effect following oral antipsychotic treatment (without washout period). Primary efficacy endpoint was percentage of patients with ≥30% improvement in the PANSS total score at the end of 13 weeks. Secondary efficacy endpoints included change from baseline to end of week 13 in PANSS total score, PANSS subscale scores, Marder factor scores, Clinical Global Impressions-Severity score, and Personal and Social Performance Scale scores. Overall, 477/610 enrolled patients (full analysis set, 78.2%) completed the study (men: 55.1%; women: 44.9%; mean age: 31.5 years). Total, 443/610 (72.6%, full analysis set) patients achieved primary endpoint (mean [standard deviation] change from baseline: -30.9 [19.51]). All secondary endpoints demonstrated significant improvement at the end of 13 weeks. One death occurred during this acute phase. The most common (>5%) treatment-emergent adverse events were extrapyramidal disorders (8.4%). The efficacy and safety data are consistent with other short-term, placebo-controlled studies of paliperidone palmitate conducted in similar populations.

  3. Postural and Balance Disorders in Patients with Parkinson's Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment

    PubMed Central

    Santamato, Andrea; Ranieri, Maurizio; Cinone, Nicoletta; Stuppiello, Lucia Anna; Valeno, Giovanni; De Sanctis, Jula Laura; Fortunato, Francesca; Solfrizzi, Vincenzo; Greco, Antonio; Seripa, Davide; Panza, Francesco

    2015-01-01

    Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson's disease (PD) to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy) for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients. PMID:26798551

  4. Collagenase clostridium histolyticum in patients with Dupuytren’s contracture: results from POINT X, an open-label study of clinical and patient-reported outcomes

    PubMed Central

    Arner, M.; Pajardi, G.; Reichert, B.; Szabo, Z.; Masmejean, E. H.; Fores, J.; Chapman, D. S.; Gerber, R. A.; Huard, F.; Seghouani, A.; Szczypa, P. P.

    2015-01-01

    In POINT X, a study designed to reflect clinical practice and patient treatment choices, 254 European patients received open-label collagenase for Dupuytren’s contracture. The most severely affected joint was treated first in 74% of patients. In total, 52%, 41%, 7%, and 1% of patients selected the little, ring, middle, and index finger, respectively; 79% had one or two joints treated. Only 9% of patients (n = 24) received 4 or 5 injections. The mean improvement in total passive extension deficit (TPED) was 34° on day 1, improving further by day 7 to 42°. This secondary improvement was maintained by day 90 and month 6. The mean number of injections/joint was 1.2 for the metacarpophalangeal joint and 1.25 for the proximal interphalangeal joint. Median time to recovery was 4 days; the mean improvement in hand function was clinically relevant as measured by the Unité Rhumatologique des Affections de la Main (URAM) score. In total, 87% and 86% of patients and physicians, respectively, were very satisfied or satisfied with treatment at month 6, although correlation between TPED and patient satisfaction was weak (Spearman −0.18, 95% CI −0.32 to −0.06). Collagenase was well tolerated, with 10 (3.9%) patients experiencing severe adverse events. As a real-world study, the POINT X findings can be generalized to the at-large population. PMID:24470559

  5. Safety and performance of cohesive polydensified matrix hyaluronic acid fillers with lidocaine in the clinical setting – an open-label, multicenter study

    PubMed Central

    Kühne, Ulrich; Esmann, Jørgen; von Heimburg, Dennis; Imhof, Matthias; Weissenberger, Petra; Sattler, Gerhard

    2016-01-01

    Cohesive polydensified matrix (CPM®) hyaluronic acid fillers are now available with or without lidocaine. The aim of this study was to investigate the safety and performance of CPM® fillers with lidocaine in the clinical setting. In an open-label, prospective, postmarketing study, 108 patients from seven sites in Germany and Denmark were treated with one or more lidocaine-containing CPM® fillers. Performance was assessed using the Merz Aesthetics Scales® (MAS). Pain was rated on an 11-point visual analog scale. Patients’ and physicians’ satisfaction as well as adverse events were recorded. Improvements of ≥1-point on MAS immediately after and 17 days posttreatment were observed in ~90% of patients compared with baseline. All investigators assessed ejection force, product positioning, and performance as similar or superior to the respective nonlidocaine products. Overall, 94% of investigators were satisfied with the esthetic outcomes and were willing to continue using the products. All patients except one were satisfied with the results, and all were willing to repeat the treatment. Mean pain scores were low during (<3.0) and after injection (<0.6). Except for one case of bruising, all adverse events were mild to moderate. CPM® fillers with lidocaine are safe and effective for a wide range of esthetic facial indications. PMID:27799807

  6. Effect of osmotic-release oral system methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder: an open-label study.

    PubMed

    Na, Kyoung-Sae; Lee, Soyoung Irene; Hong, Sungdo David; Kim, Ji-Hoon; Shim, Se-Hoon; Choi, Jeewook; Yang, Jaewon; Lee, Moon-Soo; Joung, Yoo-Sook; Kim, Eui-Jung; Park, Joon-Ho

    2013-07-01

    We evaluated the effect of osmotic-release oral system (OROS) methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder (ADHD). In an open-label study, 121 adolescents with ADHD were administered flexible doses of OROS methylphenidate for 12 weeks. The efficacy of methylphenidate on ADHD symptoms was evaluated by ADHD Rating Scale (ARS) and Clinical Global Impression Scale (CGI). Learning Skills Test (LST) was used to measure the learning skills of the participants at the baseline and the endpoint. Continuous performance test, visuospatial and verbal working memory, verbal fluency, and inhibition were evaluated before and after the 12 weeks of treatment. The mean total and subscores of LST were significantly increased after the 12-week treatment with OROS methylphenidate. Executive functions were also improved during the trial, with the exception of inhibition measured by the Stroop Test. To the best of our knowledge, this is the first study to examine the influence of OROS methylphenidate on learning skill. As a result, OROS methylphenidate was effective in enhancing learning skills in adolescents with ADHD.

  7. Collagenase clostridium histolyticum in patients with Dupuytren's contracture: results from POINT X, an open-label study of clinical and patient-reported outcomes.

    PubMed

    Warwick, D; Arner, M; Pajardi, G; Reichert, B; Szabo, Z; Masmejean, E H; Fores, J; Chapman, D S; Gerber, R A; Huard, F; Seghouani, A; Szczypa, P P

    2015-02-01

    In POINT X, a study designed to reflect clinical practice and patient treatment choices, 254 European patients received open-label collagenase for Dupuytren's contracture. The most severely affected joint was treated first in 74% of patients. In total, 52%, 41%, 7%, and 1% of patients selected the little, ring, middle, and index finger, respectively; 79% had one or two joints treated. Only 9% of patients (n = 24) received 4 or 5 injections. The mean improvement in total passive extension deficit (TPED) was 34° on day 1, improving further by day 7 to 42°. This secondary improvement was maintained by day 90 and month 6. The mean number of injections/joint was 1.2 for the metacarpophalangeal joint and 1.25 for the proximal interphalangeal joint. Median time to recovery was 4 days; the mean improvement in hand function was clinically relevant as measured by the Unité Rhumatologique des Affections de la Main (URAM) score. In total, 87% and 86% of patients and physicians, respectively, were very satisfied or satisfied with treatment at month 6, although correlation between TPED and patient satisfaction was weak (Spearman -0.18, 95% CI -0.32 to -0.06). Collagenase was well tolerated, with 10 (3.9%) patients experiencing severe adverse events. As a real-world study, the POINT X findings can be generalized to the at-large population.

  8. Improvement in social and cognitive functioning associated with paliperidone extended-release treatment in patients with schizophrenia: a 24-week, single arm, open-label study

    PubMed Central

    Shi, Chuan; Yao, Shu Qiao; Xu, Yi Feng; Shi, Jian Guo; Xu, Xiu Feng; Zhang, Cong Pei; Jin, Hua; Yu, Xin

    2016-01-01

    Purpose This single-arm, open-label study aimed to explore the effects of extended-release paliperidone on social and cognitive function in patients with schizophrenia. Methods Paliperidone extended-release (flexible dose ranging from 3 to 12 mg/day orally) was administered for 24 weeks in patients with schizophrenia. Patient function was assessed using the personal and social performance scale, measurement and treatment research to improve cognition in schizophrenia initiative-consensus cognitive battery, positive and negative syndrome scale, and clinical global impression-severity. Results Ninety patients were included in the full analysis set, while 72 patients were included in the per protocol set. The personal and social performance score was 54.3±14.3 at baseline, and significantly increased to 73.4±12.6 at week 24 (P<0.001). For the measurement and treatment research to improve cognition in schizophrenia initiative-consensus cognitive battery assessment, six of the nine individual subtests, six of the seven cognitive domains, and total cognitive scores improved significantly (P<0.05) between baseline and endpoint. positive and negative syndrome scale total scores and clinical global impression-severity scores decreased gradually (P<0.001) from week 4 to the conclusion of the study. Conclusion Paliperidone extended-release treatment significantly improves social and neurocognitive function as well as symptoms in Chinese patients with schizophrenia. PMID:27601904

  9. Improvement in social and cognitive functioning associated with paliperidone extended-release treatment in patients with schizophrenia: a 24-week, single arm, open-label study

    PubMed Central

    Shi, Chuan; Yao, Shu Qiao; Xu, Yi Feng; Shi, Jian Guo; Xu, Xiu Feng; Zhang, Cong Pei; Jin, Hua; Yu, Xin

    2016-01-01

    Purpose This single-arm, open-label study aimed to explore the effects of extended-release paliperidone on social and cognitive function in patients with schizophrenia. Methods Paliperidone extended-release (flexible dose ranging from 3 to 12 mg/day orally) was administered for 24 weeks in patients with schizophrenia. Patient function was assessed using the personal and social performance scale, measurement and treatment research to improve cognition in schizophrenia initiative-consensus cognitive battery, positive and negative syndrome scale, and clinical global impression-severity. Results Ninety patients were included in the full analysis set, while 72 patients were included in the per protocol set. The personal and social performance score was 54.3±14.3 at baseline, and significantly increased to 73.4±12.6 at week 24 (P<0.001). For the measurement and treatment research to improve cognition in schizophrenia initiative-consensus cognitive battery assessment, six of the nine individual subtests, six of the seven cognitive domains, and total cognitive scores improved significantly (P<0.05) between baseline and endpoint. positive and negative syndrome scale total scores and clinical global impression-severity scores decreased gradually (P<0.001) from week 4 to the conclusion of the study. Conclusion Paliperidone extended-release treatment significantly improves social and neurocognitive function as well as symptoms in Chinese patients with schizophrenia.

  10. A randomized, open-label, multicentre study to evaluate plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus and arteriosclerosis obliterans when treated with Probucol and Cilostazol

    PubMed Central

    Ma, Xiao-Wei; Guo, Xiao-Hui; Xiao, Xin-Hua; Guo, Li-Xin; Lv, Xiao-Feng; Li, Quan-Min; Gao, Yan

    2012-01-01

    Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus (T2DM) and arteriosclerosis obliteran (ASO) when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40–75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized patients, 165 for per-protocol and 160 for the safety (QTc intervals) were set, respectively. Probucol significantly reduced total cholesterol (P < 0.001), low-density lipoprotein cholesterol (LDL-C), (P = 0.01), and high-density lipoprotein cholesterol (HDL-C) (P < 0.001) compared with conventional therapy. Cilostazol was effective in increasing HDL-C (P = 0.002) and reducing triglycerides levels (P < 0.01) compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein (Ox-LDL, P = 0.065). No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies. PMID:23097651

  11. Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore.

    PubMed

    Ooi, Y P; Weng, S-J; Jang, L Y; Low, L; Seah, J; Teo, S; Ang, R P; Lim, C G; Liew, A; Fung, D S; Sung, M

    2015-08-01

    The goal of this open-label trial was to examine the efficacy and safety of a 12-week omega-3 fatty acids supplementation among children suffering with Autism Spectrum Disorders (ASD). A total of 41 children and adolescents aged 7-18 years (36 boys, 5 girls; mean age = 11.66, s.d. = 3.05) diagnosed with ASD participated in the study. At post-treatment, participants showed significant improvements on all subscales of the Social Responsiveness Scale (P < 0.01) and the Social and Attention Problems syndrome scales of the Child Behavior Checklist (P < 0.05). Blood fatty acid levels were significantly correlated with changes in the core symptoms of ASD. Baseline levels of blood fatty acid levels were also predictive of response to the omega-3 treatment. Omega-3 fatty acids supplementation was well-tolerated and did not cause any serious side effects. Our findings lend some preliminary support for the use of omega-3 fatty acids supplementation in addressing ASD. Future randomized controlled trials of omega-3 fatty acids in ASD with blood fatty acid measurements with a larger sample and longer follow-up period is warranted.

  12. Evaluation of clinical efficacy and safety of once daily topical administration of 1% oxiconazole cream and lotion in dermatophytosis : an open label, non comparative multicentre study.

    PubMed

    Jerajani, H R; Amladi, S T; Bongale, R; Adepu, V; Tendolkar, U M; Sentamilselvi, G; Janaki, V R; Janaki, C; Vidhya, S; Marfatia, Y S; Patel, K; Sharma, N; Cooverji, N D

    2000-01-01

    The clinical efficacy and safety of once daily topical administration of 1% oxiconazole cream and lotion was assessed in an open label, non comparative trial in tinea cruris, tinea corporis and tinea pedis patients. In treated patients, severity scores of erythema, pruritus, scaling, vesicles, papules and burning showed a progressive fall over a period of 4 weeks at all the study centres. With lotion, mean percentage improvement of symptoms varied from 35% (week 1) to 87.6 - 98.7% (week 4). With cream, it varied from 35% (week 1) to 82.5 - 99.5% (week 4). Overall global evaluation response showed clear, excellent and good response in 60%, 21% and 17% of the patients treated with lotion respectively. With cream, excellent and good response was observed in 71%, 10% and 16% of the patients respectively. In T. pedis patients, clear, excellent and good response was observed in 4/8, 2/8 and 1/8 patients respectively with lotion. Cream showed clear (8/15), excellent (4/15) and good (1/15) in these patients. None of the patients out of 178 enrolled, reported any side effect during the trial.

  13. A Complex Multiherbal Regimen Based on Ayurveda Medicine for the Management of Hepatic Cirrhosis Complicated by Ascites: Nonrandomized, Uncontrolled, Single Group, Open-Label Observational Clinical Study

    PubMed Central

    Patel, Manish V.; Patel, Kalapi B.; Gupta, Shivenarain; Michalsen, Andreas; Stapelfeldt, Elmar; Kessler, Christian S.

    2015-01-01

    Hepatic cirrhosis is one of the leading causes of death worldwide, especially if complicated by ascites. This chronic condition can be related to the classical disease entity jalodara in Traditional Indian Medicine (Ayurveda). The present paper aims to evaluate the general potential of Ayurvedic therapy for overall clinical outcomes in hepatic cirrhosis complicated by ascites (HCcA). In form of a nonrandomized, uncontrolled, single group, open-label observational clinical study, 56 patients fulfilling standardized diagnostic criteria for HCcA were observed during their treatment at the P. D. Patel Ayurveda Hospital, Nadiad, India. Based on Ayurvedic tradition, a standardized treatment protocol was developed and implemented, consisting of oral administration of single and compound herbal preparations combined with purificatory measures as well as dietary and lifestyle regimens. The outcomes were assessed by measuring liver functions through specific clinical features and laboratory parameters and by evaluating the Child-Pugh prognostic grade score. After 6 weeks of treatment and a follow-up period of 18 weeks, the outcomes showed statistically significant and clinically relevant improvements. Further larger and randomized trials on effectiveness, safety, and quality of the Ayurvedic approach in the treatment of HCcA are warranted to support these preliminary findings. PMID:26339267

  14. Safety, Tolerability, and Efficacy of Tocilizumab in Rheumatoid Arthritis: An Open-Label Phase 4 Study in Patients from the Middle East

    PubMed Central

    Hammoudeh, Mohammed; Al Awadhi, Adel; Hasan, Eman Haji; Akhlaghi, Maassoumeh; Ahmadzadeh, Arman; Sadeghi Abdollahi, Bahar

    2015-01-01

    This open-label study investigated the safety and efficacy of tocilizumab in Middle Eastern patients with rheumatoid arthritis (RA). Patients whose Disease Activity Score based on 28 joints (DAS28) was >3.2 received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks. Patients receiving aTNF ± nonbiologic disease-modifying antirheumatic drug(s) (DMARD(s)) switched to tocilizumab; patients receiving nonbiologic DMARD monotherapy added tocilizumab. Primary end points were adverse events (AEs), serious AEs (SAEs), and laboratory parameters; secondary end points were DAS28, Health Assessment Questionnaire-Disability Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Eighty-eight of 95 patients completed 24 weeks. Overall, 125 AEs were reported in 43 (45%) patients; the most common were increased hepatic enzymes (16%) and cholesterol (11%). Eight patients experienced SAEs. Significant changes from baseline to week 24 occurred for hemoglobin, neutrophils, platelets, total cholesterol, and liver enzymes (P < 0.05). DAS28, CRP, and ESR decreased significantly from baseline at each visit (P < 0.0001). At week 24, the proportions of patients reporting DAS28 clinically meaningful improvement (decrease ≥1.2), low disease activity (DAS28 ≥2.6 to ≤3.2), and remission (DAS28 <2.6) were 92%, 23%, and 64%, respectively. Safety and efficacy of tocilizumab were consistent with values reported in Western patients. PMID:26089907

  15. Effectiveness of a single application of 0·25% fipronil solution for the treatment of hirstiellosis in captive green iguanas (Iguana iguana): an open-label study.

    PubMed

    Farmaki, Rania; Simou, Chrisa; Papadopoulos, Elias; Koutinas, Alexander F; Saridomichelakis, Manolis N

    2013-08-01

    Hirstiella spp. are common ectoparasites of captive green iguanas (Iguana iguana). Suggested treatments are empirical and some of them are of low efficacy and potentially toxic. The objective of this open-label study was to investigate the short-term efficacy and safety of a single application of 0·25% fipronil solution for the treatment of hirstiellosis. The skin of 50 green iguanas was thoroughly examined with the aid of bright light and magnifying lenses. A total of 21 iguanas were found to be infested, harbouring 1-24 mites (median: 5). All 35 mites collected from 17 iguanas were identified as Hirstiella sp. Both infested and non-infested lizards, sharing the same enclosure, were carefully wiped with 0·25% fipronil solution. The safety and the efficacy of the treatment were evaluated after 2 days in 47/50 (94%) and 7 days in 29/50 (58%) iguanas. Compared with pre-treatment levels, the parasitic load did not changed significantly on the second day but was significantly lower on day 7 (P = 0·006). No adverse reactions were noticed. Based on these results a single whole-body application of 0·25% fipronil solution can be considered a safe and effective treatment for the reduction of parasitic burden in captive green iguanas infested by Hirstiella sp. mites.

  16. Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study.

    PubMed

    Handley, Alison; Lloyd, Eric; Roberts, Andrew; Barger, Bruce

    2016-01-01

    This 56-week phase 3, open-label, treat-to-target study, involving 2 consecutive, non-randomized cohorts, evaluated the safety and tolerability of azilsartan medoxomil (AZL-M) in essential hypertension (mean baseline blood pressure [BP] 152/100 mmHg). All subjects (n = 669) initiated AZL-M 40 mg QD, force-titrated to 80 mg QD at week 4, if tolerated. From week 8, subjects could receive additional medications, starting with chlorthalidone (CLD) 25 mg QD (Cohort 1) or hydrochlorothiazide (HCTZ) 12.5-25 mg QD (Cohort 2), if required, to reach BP targets. Adverse events (AEs) were reported in 75.9% of subjects overall in the two cohorts (73.8% Cohort 1, 78.5% Cohort 2). The most common AEs were dizziness (14.3%), headache (9.9%) and fatigue (7.2%). Transient serum creatinine elevations were more frequent with add-on CLD. Clinic systolic/diastolic BP (observed cases at week 56) decreased by 25.2/18.4 mmHg (Cohort 1) and 24.2/17.9 mmHg (Cohort 2). These results demonstrate that AZL-M is well tolerated over the long term and provides stable BP improvements when used in a treat-to-target BP approach with thiazide-type diuretics. PMID:26817604

  17. Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study

    PubMed Central

    Handley, Alison; Lloyd, Eric; Roberts, Andrew; Barger, Bruce

    2016-01-01

    Abstract This 56-week phase 3, open-label, treat-to-target study, involving 2 consecutive, non-randomized cohorts, evaluated the safety and tolerability of azilsartan medoxomil (AZL-M) in essential hypertension (mean baseline blood pressure [BP] 152/100 mmHg). All subjects (n = 669) initiated AZL-M 40 mg QD, force-titrated to 80 mg QD at week 4, if tolerated. From week 8, subjects could receive additional medications, starting with chlorthalidone (CLD) 25 mg QD (Cohort 1) or hydrochlorothiazide (HCTZ) 12.5–25 mg QD (Cohort 2), if required, to reach BP targets. Adverse events (AEs) were reported in 75.9% of subjects overall in the two cohorts (73.8% Cohort 1, 78.5% Cohort 2). The most common AEs were dizziness (14.3%), headache (9.9%) and fatigue (7.2%). Transient serum creatinine elevations were more frequent with add-on CLD. Clinic systolic/diastolic BP (observed cases at week 56) decreased by 25.2/18.4 mmHg (Cohort 1) and 24.2/17.9 mmHg (Cohort 2). These results demonstrate that AZL-M is well tolerated over the long term and provides stable BP improvements when used in a treat-to-target BP approach with thiazide-type diuretics. PMID:26817604

  18. Peyronie's disease and low intensity shock wave therapy: Clinical outcomes and patient satisfaction rate in an open-label single arm prospective study in Australian men

    PubMed Central

    2015-01-01

    Purpose To evaluate the efficacy, safety and patient satisfaction outcomes following low intensity extracorporeal shock wave therapy (LiESWT) in men with Peyronie's disease (PD) using a standardised protocol. Materials and Methods In this open-label single arm prospective study, patients with PD were enrolled following informed consent. Patient demographics, change in penile curvature and plaque hardness, International Index of Erectile Function (IIEF)-5 score, and overall satisfaction score (on a 5-point scale) were recorded. Treatment template consists of 3000 shock waves to the Peyronie's plaque over 20 minutes, twice weekly for 6 weeks. Results The majority of patients have PD history longer than 6 months (mean, 12.8 months; range, 6-28 months). Two thirds of patients have received and failed oral medical therapy. There were improvements in penile curvature (more than 15 degrees in 33% of men), plaque hardness (60% of men) and penile pain (4 out of 6 men) following LiESWT. There was a moderate improvement in IIEF-5 score (>5 points reported in 20% of men). No complication was reported and the majority of patients were satisfied (rated 4 out of 5; 70% of men) and would recommend this therapy to others. Conclusions In a carefully selected group of men with PD, LiESWT appears to be safe, has moderate efficacy and is associated with high patient satisfaction rate in the short term. PMID:26568796

  19. No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a Phase I Open Label Study to assess safety, tolerability and cytokine responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed since the mid 1990s by between 2 and 5 million people daily, the scientific literature lacks rigorous clinical trials that describe the potential harms of LGG, particularly in the elderly. The primary objective of this open label...

  20. Anxiety Sensitivity and Panic Attacks: A 1-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Li, Wen; Zinbarg, Richard E.

    2007-01-01

    The hypothesis that anxiety sensitivity (AS) is a risk factor for panic genesis has obtained compelling support, but the clinical/practical importance of AS in panic genesis has been questioned. In addition, the association between panic experience and AS increase has not been clearly demonstrated. Through this 1-year longitudinal study among…

  1. Efficacy of Atomoxetine in Children with Severe Autistic Disorders and Symptoms of ADHD: An Open-Label Study

    ERIC Educational Resources Information Center

    Charnsil, Chawanun

    2011-01-01

    Objective: This study aims to examine the efficacy of atomoxetine in treating symptoms of attention deficit hyperactivity disorder (ADHD) in children with severe autistic disorder. Method: Children with severe autistic disorder who had symptoms of ADHD were given atomoxetine for 10 weeks. The efficacy of atomoxetine was evaluated by using the…

  2. An Open-Label Study of Controlled-Release Melatonin in Treatment of Sleep Disorders in Children with Autism

    ERIC Educational Resources Information Center

    Giannotti, F.; Cortesi, F.; Cerquiglini, A.; Bernabei, P.

    2006-01-01

    Long-term effectiveness of controlled-release melatonin in 25 children, aged 2.6-9.6 years with autism without other coexistent pathologies was evaluated openly. Sleep patterns were studied using Children's Sleep Habits Questionnaire (CSHQ) and sleep diaries at baseline, after 1-3-6 months melatonin treatment and 1 month after discontinuation.…

  3. Levetiracetam extended release for the treatment of patients with partial-onset seizures: A long-term, open-label follow-up study.

    PubMed

    Chung, Steve; Ceja, Hugo; Gawłowicz, Jacek; McShea, Cindy; Schiemann, Jimmy; Lu, Sarah

    2016-02-01

    This was an open-label study (N01281 [NCT00419393]) assessing the long-term safety of extended-release levetiracetam (LEV XR) in patients with partial-onset seizures (POS); the study was a follow-up to a double-blind, randomized, historical controlled, multicenter, conversion to monotherapy study (N01280 [NCT00419094]). Eligible patients initially received LEV XR 2000 mg/day; dose adjustments and the addition of other antiepileptic drugs (AEDs) were permitted. Overall, 190 patients were enrolled, 189 (99.5%) received LEV XR (safety and efficacy populations) and 166 patients (87.4%) completed the study. The study duration in completed patients was 5.5-24.6 months. Mean daily dose of LEV XR was 2131 mg/day. Treatment-emergent adverse events (TEAEs) occurred in 126 patients (66.7%); most were of mild or moderate severity. Five patients (2.6%) had a TEAE that led to treatment discontinuation. Treatment-emergent serious adverse events occurred in 22 patients (11.6%). Twenty-six patients (13.8%) experienced a psychiatric TEAE. The median 7-day normalized POS frequency was: 1.38 at N01280 study baseline; 0.50 at the first visit of N01281 (last visit of N01280); and 0.00-0.36 between all subsequent visits. Overall, 171 patients (90.5%) entered the N01281 study on LEV XR monotherapy; 65.3% (32/49) of patients remained on monotherapy for 12 months and 47.1% (8/17) for 18 months. While remaining on LEV XR monotherapy, 27/139 patients (19.4%) were seizure-free at 6 months and 8/49 (16.3%) at 12 months. In conclusion, LEV XR was well tolerated when administered as long-term monotherapy or in combination with other AEDs in patients with inadequately controlled POS. PMID:26716580

  4. Role of antioxidant property of carvedilol in mild to moderate hypertensive patients: A prospective open-label study

    PubMed Central

    Ayashi, Saleh; Assareh, Ahmad Reza; Jalali, Mohammad Taha; Olapour, Samaneh; Yaghooti, Hamid

    2016-01-01

    Objective: Carvedilol is a nonselective third generation β-blocker that does not display the negative effects of traditional β-blockers. Regarding the antioxidant, anti-inflammatory and distinct metabolic properties of carvedilol which are similar to that of high-density lipoprotein (HDL) and paraoxonase 1 (PON1), the present study intends to investigate the effects of carvedilol treatment on malondialdehyde (MDA) and soluble lectin-like ox-low-density lipoprotein (LDL) receptor (sLOX-1) as markers of oxidative stress in association to lipid profiles, apolipoproteins (apo), and PON1 activity in hypertensive patients. Patients and Methods: This clinical trial study was performed on forty patients with mild to moderate essential hypertension. Subjects were studied before and after 2 months treatment with carvedilol, 25 mg daily. Lipids and lipoproteins were measured using a biochemistry analyzer. PON and arylesterase activity were assayed using paraoxon and phenyl acetate as substrates, respectively. MDA was quantified using a chemical colorimetric assay. ELISA was used to measure sLOX-1. Results: Our results showed that carvedilol treatment decreased systolic and diastolic blood pressure as much as forty and 16 mmHg, respectively (P < 0.001). It also increased HDL, total cholesterol, and serum PON1 activity (P < 0.05), but the levels of triglyceride, LDL, apo A-I, and apo B did not significantly change. There was an inverse correlation between serum PON1 activity and serum MDA. Conclusion: This study confirmed the antihypertensive effect of the drug and its beneficial metabolic effects through augmenting HDL and PON1 activity. We propose that the antioxidant effects of carvedilol can be partially attributed to increased PON-1 activity. PMID:27756946

  5. A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.

    PubMed

    Oritani, Kenji; Okamoto, Shinichiro; Tauchi, Tetsuzo; Saito, Shigeki; Ohishi, Kohshi; Handa, Hiroshi; Takenaka, Katsuto; Gopalakrishna, Prashanth; Amagasaki, Taro; Ito, Kazuo; Akashi, Koichi

    2015-03-01

    Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated rapid and durable improvements in splenomegaly and symptoms and a survival benefit in 2 phase 3 trials in patients with myelofibrosis. Ruxolitinib was well tolerated and effectively reduced splenomegaly and symptom burden in Asian patients with myelofibrosis in the Asian multinational, phase 2 Study A2202. We present a subset analysis of Japanese patients (n = 30) in Study A2202. At data cutoff, 22 patients were ongoing; 8 discontinued, mainly due to adverse events (n = 4). At week 24, 33 % of patients achieved ≥35 % reduction from baseline in spleen volume; 56.0 % achieved ≥50 % reduction from baseline in total symptom score, as measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0. The most common adverse events were anemia (63 %), thrombocytopenia (40 %), nasopharyngitis (37 %), decreased platelet counts (30 %), and diarrhea (30 %). Dose reductions or interruptions due to hemoglobin decreases were more frequent in Japanese patients; no loss of efficacy and no discontinuations due to hematologic abnormalities were observed. Ruxolitinib was well tolerated in Japanese patients and provided substantial reductions in splenomegaly and myelofibrosis-related symptoms similar to those observed in the overall Asian population and phase 3 COMFORT studies.

  6. Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study

    PubMed Central

    Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

    2015-01-01

    Abstract Objectives: Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. Design: This study was a single-arm, open-label pilot study. Subjects: Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Intervention: Participants took 5.6×1010 colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Outcome measures: Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Results: Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. Conclusions: In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease. PMID:25893960

  7. Open-Label Crossover Study of Primaquine and Dihydroartemisinin-Piperaquine Pharmacokinetics in Healthy Adult Thai Subjects

    PubMed Central

    Hanboonkunupakarn, Borimas; Ashley, Elizabeth A.; Jittamala, Podjanee; Tarning, Joel; Pukrittayakamee, Sasithon; Hanpithakpong, Warunee; Chotsiri, Palang; Wattanakul, Thanaporn; Panapipat, Salwaluk; Lee, Sue J.; Day, Nicholas P. J.

    2014-01-01

    Dihydroartemisinin-piperaquine is an artemisinin-based combination treatment (ACT) recommended by the WHO for uncomplicated Plasmodium falciparum malaria, and it is being used increasingly for resistant vivax malaria where combination with primaquine is required for radical cure. The WHO recently reinforced its recommendations to add a single dose of primaquine to ACTs to reduce P. falciparum transmission in low-transmission settings. The pharmacokinetics of primaquine and dihydroartemisinin-piperaquine were evaluated in 16 healthy Thai adult volunteers in a randomized crossover study. Volunteers were randomized to two groups of three sequential hospital admissions to receive 30 mg (base) primaquine, 3 tablets of dihydroartemisinin-piperaquine (120/960 mg), and the drugs together at the same doses. Blood sampling was performed over 3 days following primaquine and 36 days following dihydroartemisinin-piperaquine dosing. Pharmacokinetic assessment was done with a noncompartmental approach. The drugs were well tolerated. There were no statistically significant differences in dihydroartemisinin and piperaquine pharmacokinetics with or without primaquine. Dihydroartemisinin-piperaquine coadministration significantly increased plasma primaquine levels; geometric mean ratios (90% confidence interval [CI]) of primaquine combined versus primaquine alone for maximum concentration (Cmax), area under the concentration-time curve from 0 h to the end of the study (AUC0–last), and area under the concentration-time curve from 0 h to infinity (AUC0–∞) were 148% (117 to 187%), 129% (103 to 163%), and 128% (102 to 161%), respectively. This interaction is similar to that described recently with chloroquine and may result in an enhanced radical curative effect. (This study has been registered at ClinicalTrials.gov under registration no. NCT01525511.) PMID:25267661

  8. Fenofibrate improves endothelial function and plasma myeloperoxidase in patients with type 2 diabetes mellitus: an open-label interventional study

    PubMed Central

    2014-01-01

    Background Fenofibrate offers a number of benefits on the cardiovascular system and it is plausible that its anti-inflammatory, anti-oxidant and anti-fibrotic effects and enhancement of cardiac metabolic performances may account for its direct cardioprotective effects. In this study we aimed to investigate the effect of fenofibrate on endothelial function assesed by vascular studies and levels of soluble E-selectin (sE-selectin) as well as the effect on plasma myeloperoxidase (MPO) in patients with type 2 diabetes mellitus (T2DM) without previous use of lipid-lowering medication. Methods 27 patients (14 men and 13 women) with T2DM and good glycemic control (HbA1c: min 5.9%, max: 7.1%) treated with metformin monotherapy, without previous use of lipid-lowering medication were enrolled in this study. Vascular studies included measures of brachial artery diameter before and after release of a suprasystolic ischemia. FMD was calculated as the percent (%) change in arterial diameter following reactive hyperemia. Student’s paired t test and Wilcoxon Signed Ranks Test were used to compare values before and after fenofibrate therapy. Results Fenofibrate therapy significantly increased post ischemia mean brachial artery diameter at 60 s (from 4.7 [4.4; 5.0] mm to 4.9 [4.6; 5.2] mm, p = 0.01) and at 90 s (from 4.7 [4.4; 5.0] mm to 4.9 [4.6; 5.1], p = 0.02). FMD response to hyperaemia at 60 s increased with 4.5 ± 13.7% (median value pre- treatment: 22.2%, median value post- treatment 25.0%, z = −2.9, p = 0.004). After 8 weeks of fenofibrate therapy, plasma MPO levels decreased to 49.5 [30.3; 71.5] ng/ml (% change from baseline = 4.6%, z = −2.2, p = 0.03) and mean plasma sE-selectin levels decreased to 67.1 [54.4; 79.8] ng/ml, (% change from baseline = 2.6%, p = 0.03). Conclusion In patients with T2DM without previous treatment for dyslipidemia, short-term treatment with fenofibrate improved vascular endothelial function as demonstrated by increased post ischemia mean

  9. Re-treatment of relapsed Paget's disease of bone with zoledronic acid: results from an open-label study.

    PubMed

    Reid, Ian R; Brown, Jacques P; Levitt, Naomi; Román Ivorra, José A; Bachiller-Corral, Javier; Ross, Ian L; Su, Guoqin; Antunez-Flores, Oscar; Aftring, R Paul

    2013-01-01

    Six patients from the phase 3 trials of zoledronic acid in Paget's disease, who had received zoledronic acid initially and had subsequently relapsed, were entered into an open re-treatment study. Following re-treatment, each patient reached similar absolute nadirs of serum alkaline phosphatase to those recorded after their first dose. No significant adverse events were reported. It is concluded that, while re-treatment of Paget's disease with zoledronic acid is rarely needed, it is safe and effective, with no evidence of treatment resistance based on this small cohort. PMID:24422139

  10. A randomized, comparative, open-label study of efficacy and tolerability of alfuzosin, tamsulosin and silodosin in benign prostatic hyperplasia

    PubMed Central

    Manjunatha, R.; Pundarikaksha, H. P.; Madhusudhana, H. R.; Amarkumar, J.; Hanumantharaju, B. K.

    2016-01-01

    Objectives: Benign prostatic hyperplasia (BPH) is a common and progressive disease affecting elderly males, often associated with lower urinary tract symptoms (LUTS). α1-blockers are the mainstay in symptomatic therapy of BPH. Because of their greater uroselectivity and minimal hemodynamic effects, alfuzosin, tamsulosin, and silodosin are generally preferred. The aim of this study was to compare the efficacy and tolerability of alfuzosin, tamsulosin, and silodosin in patients with BPH and LUTS. Methods: Ninety subjects with BPH and LUTS were randomized into three groups of thirty in each, to receive alfuzosin sustained release (SR) 10 mg, tamsulosin 0.4 mg, or silodosin 8 mg for 12 weeks. The primary outcome measure was a change in the International Prostate Symptom Score (IPSS), and the secondary outcome measures were changes in individual subjective symptom scores, quality of life score (QLS), and peak flow rate (Qmax) from baseline. The treatment response was monitored at 2, 4, 8, and 12 weeks. Results: IPSS improved by 88.18%, 72.12%, and 82.23% in alfuzosin SR, tamsulosin and silodosin groups (P < 0.001) at 12 weeks. Improvement in QLS was >75% in all the three groups (P < 0.001). A significant improvement in Qmax was seen with alfuzosin and tamsulosin (P = 0.025 and P < 0.001) but not with silodosin (P = 0.153). However, the intergroup differences in IPSS, QLS, and Qmax were not significant. Ejaculatory dysfunction was more common with silodosin and corrected QT (QTc) prolongation occurred only with alfuzosin (two subjects) and tamsulosin (three subjects). Conclusion: Alfuzosin, tamsulosin, and silodosin showed similar efficacy in improvement of LUTS secondary to BPH, with good tolerability, acceptability, and minimum hemodynamic adverse effects. Alfuzosin, tamsulosin, and silodosin are comparable in efficacy in symptomatic management of BPH. The occurrence of QTc prolongation in three subjects with tamsulosin in the present study is an unexpected adverse

  11. Effects of Shakuyaku-Kanzo-to on Extrapyramidal Symptoms During Antipsychotic Treatment: A Randomized, Open-Label Study.

    PubMed

    Ota, Takafumi; Miura, Itaru; Kanno-Nozaki, Keiko; Hoshino, Hiroshi; Horikoshi, Sho; Fujimori, Haruo; Kanno, Tomoyuki; Mashiko, Hirobumi; Yabe, Hirooki

    2015-06-01

    Extrapyramidal symptoms (EPS) are common adverse effects of antipsychotic treatment. This study examined the effects of the traditional Japanese herbal medicine (kampo) shakuyaku-kanzo-to on EPS during antipsychotic treatment. Twenty-two Japanese patients with psychiatric disorders who had developed EPS during antipsychotic treatment were randomly allocated to receive either shakuyaku-kanzo-to (7.5 g/d) or biperiden (3 mg/d) for 2 weeks. Extrapyramidal symptoms were evaluated using the Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) and the Barnes Akathisia Rating Scale. Plasma levels of the monoamine metabolite homovanillic acid and serum prolactin levels were measured to investigate the mechanisms of action of shakuyaku-kanzo-to. Twenty of the 22 patients completed the study (10 patients in the shakuyaku-kanzo-to group and 10 patients in the biperiden group). There was a time effect on the Drug-Induced Extrapyramidal Symptom Scale total score (P < 0.01), suggesting that both shakuyaku-kanzo-to and biperiden decreased EPS. Notably, there was a time × drug interaction in dystonia, suggesting that shakuyaku-kanzo-to had a greater effect on dystonia compared with biperiden. No significant changes were observed in plasma homovanillic acid or serum prolactin levels after 2 weeks of treatment in either group. The effects of shakuyaku-kanzo-to on abnormal muscle tonus and dopamine D2 receptors may have contributed to improve EPS. These results suggest that shakuyaku-kanzo-to may be useful in decreasing EPS, especially dystonia, in patients undergoing treatment with antipsychotic agents.

  12. Isotonic saline in elderly men: an open-labelled controlled infusion study of electrolyte balance, urine flow and kidney function.

    PubMed

    Hahn, R G; Isacson, M Nyberg; Fagerström, T; Rosvall, J; Nyman, C R

    2016-02-01

    Isotonic saline is a widely-used infusion fluid, although the associated chloride load may cause metabolic acidosis and impair kidney function in young, healthy volunteers. We wished to examine whether these effects also occurred in the elderly, and conducted a crossover study in 13 men with a mean age of 73 years (range 66-84), who each received intravenous infusions of 1.5 l of Ringer's acetate and of isotonic saline. Isotonic saline induced mild changes in plasma sodium (mean +1.5 mmol.l(-1) ), plasma chloride (+3 mmol.l(-1) ) and standard bicarbonate (-2 mmol.l(-1) ). Three hours after starting the infusions, 68% of the Ringer's acetate and 30% of the infused saline had been excreted (p < 0.01). The glomerular filtration rate increased in response to both fluids, but more after the Ringer's acetate (p < 0.03). Pre-infusion fluid retention, as evidenced by high urinary osmolality (> 700 mOsmol.kg(-1) ) and/or creatinine (> 7 mmol.l(-1) ), was a strong factor governing the responses to both fluid loads.

  13. Noninvasive brain stimulation by radioelectric asymmetric conveyor in the treatment of agoraphobia: open-label, naturalistic study

    PubMed Central

    Mannu, Piero; Rinaldi, Salvatore; Fontani, Vania; Castagna, Alessandro; Margotti, Matteo Lotti

    2011-01-01

    Background Agoraphobia is considered to be the most serious complication of panic disorder. It involves progressive development of debilitating anxiety symptoms related to being in situations where one would be extremely embarrassed and could not be rescued in the case of a panic attack. This study aimed to investigate the efficacy of noninvasive brain stimulation using a radioelectric asymmetric conveyor (REAC) for agoraphobia. Patients and methods Twenty-three patients (3 males and 20 females) suffering from agoraphobia and without a history of panic disorder were evaluated by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and the Agoraphobia Scale (AS). The patients were subjected to two 18-session cycles of noninvasive brain stimulation with the REAC, according to an established therapeutic protocol called neuropsycho-physical optimization. Results Analyzing the anxiety and avoidance parameters of the AS after the first and second cycles of REAC treatment revealed variation in levels of response to treatment, including weak (AS item 7), moderate (AS items 10 and 13), and good responses (AS items 1–6, 8, 9, 11, 12, and 14–20). Conclusion These results highlight the potential of the REAC to treat complex clinical situations such as agoraphobia, which is typically resistant to pharmacologic treatments. Furthermore, these data show the advantages of REAC treatment, even compared with modern cognitive behavioral therapy, including a relatively rapid and “stable” clinical response (just over 6 months) and economic cost. PMID:22163156

  14. Efficacy of Vasa Avaleha and its granules on Tamaka Shwasa (bronchial asthma): Open-label randomized clinical study

    PubMed Central

    Paneliya, Ankit M.; Patgiri, Biswajyoti; Galib, R.; Prajapati, Pradeep Kumar

    2015-01-01

    Introduction: Bronchial asthma is one of the chronic inflammatory disorders of the respiratory tract causing a huge number of deaths annually. Increased industrialization and pollution are the exacerbating factors for this situation. In Ayurveda, this miserable condition is comparable with Tamaka Shwasa. Synthetic drugs provide instant symptomatic relief in cases of bronchial asthma but are known to develop certain adverse drug reactions. Considering this, the current suffering population is looking hopefully towards other systems of medicine such as Ayurveda for better relief. Ayurveda has a number of formulations to treat Tamaka Shwasa and is in practice with proven efficacy. Aims: To evaluate comparative clinical efficacy of Vasa Avaleha (VA) and its granules (GVA) in cases of Tamaka Shwasa. Materials and Methods: A total of 66 patients were registered and randomly grouped into A and B. Patients of Group A were treated with VA, while Group B with GVA at dose of 6 g twice a day with lukewarm water for the duration of 28 days. Follow-up was done after 14 days. The results were assessed in terms of clinical recovery, symptomatic relief, and pulmonary function improvement. Effect of the treatment was assessed based on subjective and objective parameters. Results: Significant improvement was observed in most of the cardinal and associated symptoms. Significant increase in peak expiratory flow rate, considerable decrease in absolute eosinophil count, and increased breath holding time were noticed. Withdrawal of modern emergency drugs, decreased frequency of attacks, improved quality of life were the major observations noticed in both groups. Conclusions: This study highlights the significance of traditional herbal formulations in noncommunicable diseases such as bronchial asthma, which can be used as an effective drug in place or along with modern drugs. PMID:27313413

  15. Comparative study of amrutbhallataka and glucosamine sulphate in osteoarthritis: Six months open label randomized controlled clinical trial

    PubMed Central

    Raut, Ashwinikumar; Bichile, Lata; Chopra, Arvind; Patwardhan, Bhushan; Vaidya, Ashok

    2013-01-01

    Background: AmrutBhallatak (ABFN02), a ‘rasayana’ drug from Ayurveda is indicated in degenerative diseases and arthritis. Objective: To evaluate safety and efficacy of ABFN02 in osteoarthritis (OA) and compare it with Glucosamine sulphate (GS) Materials and Methods: This was a randomized open comparative study. Ambulant OPD patients of OA knees (n = 112) were enrolled for 24 weeks. Tablets (750mg each) of GS and ABFN02 were matched. Three groups of patients: (A) GS, one tablet × twice/day × 24 weeks. (B) ABFN02, incremental pulse dosage (one tablet x twice/day × two weeks, two tablets × twice/day × two weeks, three tablets × twice/day × two weeks), two such cycles of drug and non-drug phases alternately for six weeks each (C) ABFN02 continuous dosage akin to GS. Pain visual analogue score (Pain-VAS) and Western Ontario and Mc-Master University Osteoarthritis Index (WOMAC) were the primary outcome measures. Secondary outcome measures were Health assessment questionnaire (HAQ), paracetamol consumption, 50 feet walking, physician and patient global assessment, knee stiffness, knee status, urinary CTX II, serum TNFa-SRI, SRII and MRI knee in randomly selected patients. Results: ABFNO2 and GS demonstrated, adherence to treatment 87.75% and 74.3%, reduction in Pain-VAS at rest 61.05% and 57.1%, reduction in pain-VAS on activity 57.4% and 59.8%, WOMAC score drop 62.8% and 59.1% respectively. Secondary outcome measures were comparable in all groups. Safety measures were also comparable. No serious adverse events reported. However, asymptomatic reversible rise in liver enzymes was noted in the ABFNO2 group. Conclusions: ABFN02 has significant activity in OA; the formulation needs further investigation. PMID:24459390

  16. Conversion to lanthanum carbonate monotherapy effectively controls serum phosphorus with a reduced tablet burden: a multicenter open-label study

    PubMed Central

    2011-01-01

    Abstract Background Lanthanum carbonate (FOSRENOL®) is an effective, well-tolerated phosphate binder. The ability of lanthanum to reduce serum phosphorus levels to ≤5.5 mg/dL in patients with end-stage renal disease (ESRD) was assessed in a clinical practice setting. Methods A 16-week, phase IV study enrolled 2763 patients at 223 US sites to evaluate the efficacy of lanthanum carbonate in controlling serum phosphorus in patients with ESRD, and patient and physician satisfaction with, and preference for, lanthanum carbonate after conversion from other phosphate-binder medications. Patients received lanthanum carbonate prescriptions from physicians. These prescriptions were filled at local pharmacies rather than obtaining medication at the clinical trial site. Changes from serum phosphorus baseline values were analyzed using paired t tests. Patient and physician preferences for lanthanum carbonate versus previous medications were assessed using binomial proportion tests. Satisfaction was analyzed using the McNemar test. Daily dose, tablet burden, and laboratory values including albumin-adjusted serum calcium, calcium × phosphorus product, and parathyroid hormone levels were secondary endpoints. Results Serum phosphorus control (≤5.5 mg/dL) was effectively maintained in patients converting to lanthanum carbonate monotherapy; 41.6% of patients had controlled serum phosphate levels at 16 weeks. Patients and physicians expressed markedly higher satisfaction with lanthanum carbonate, and preferred lanthanum carbonate over previous medication. There were significant reductions in daily dose and daily tablet burden after conversion to lanthanum carbonate. Conclusions Serum phosphorus levels were effectively maintained in patients converted from other phosphate-binder medications to lanthanum carbonate, with increased satisfaction and reduced tablet burden. Trial Registration ClinicalTrials.gov: NCT0016012 PMID:21962172

  17. Safety and immunogenicity of an AS01-adjuvanted varicella zoster virus subunit candidate vaccine (HZ/su): a phase-I, open-label study in Japanese adults.

    PubMed

    Lal, Himal; Zahaf, Toufik; Heineman, Thomas C

    2013-07-01

    An adjuvanted recombinant subunit candidate vaccine (HZ/su) containing varicella zoster virus envelope glycoprotein E was developed for the prevention of herpes zoster and its complications. This study evaluated safety and reactogenicity of HZ/su in an ethnic Japanese population. This was a phase I, open-label and single-center study conducted between March and November of 2010 in Australia. Twenty healthy ethnic Japanese subjects, aged 18-30 y and 50-69 y (1:1) were enrolled. Subjects were administered two doses of HZ/su vaccine according to a 0, 2-mo schedule. Local and general solicited symptoms were recorded for 7 d post-vaccination. Unsolicited symptoms were recorded for 30 d post-vaccination. Serious adverse events (SAEs), new onset of autoimmune disease (NOAD), other potential immune mediated disorders and HZ cases were recorded throughout the study period. All 20 subjects were included in the according-to-protocol cohort for safety. A total of 18 subjects were included in the according-to-protocol cohort for immunogenicity: 10 in the 18-30 y age group and 8 in the 50-69 y age group. The most commonly reported local and general solicited symptoms were pain and fatigue in both groups. Back pain (in the 18-30 y age group) and chills (in the 50-69 y age group) were the most frequently reported unsolicited symptoms. There were no reports of death, SAEs, NOADs, other autoimmune mediated inflammatory disorder or suspected HZ cases. This study indicated that the two-dose regimen of HZ/su exhibited a clinically acceptable safety profile in healthy young and older ethnic Japanese adults.

  18. Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation.

    PubMed

    Stoffregen, Clemens C; Odin, Elisabeth A; Carlsson, Göran U; Kurlberg, Göran K; Björkqvist, Hillevi G; Tångefjord, Maria T; Gustavsson, Bengt G

    2016-06-01

    The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study. PMID:26825869

  19. An Open-Label Randomized Crossover Trial of Lyophilized Black Raspberries on Postprandial Inflammation in Older Overweight Males: A Pilot Study.

    PubMed

    Sardo, Christine L; Kitzmiller, Joseph P; Apseloff, Glen; Harris, Robin B; Roe, Denise J; Stoner, Gary D; Jacobs, Elizabeth T

    2016-01-01

    This study was a 14-day, outpatient, open-label randomized crossover trial of lyophilized black raspberries (BRBs) in older overweight or obese males to determine whether BRB consumption affects postprandial inflammation associated with consumption of a high-fat high-calorie (HFHC) meal. Ten study participants consumed 45 g/d of lyophilized BRBs for 4 days, followed by a HFHC breakfast plus BRBs on day 6 or consumed the HFHC breakfast on day 6 without previous consumption of BRBs and then crossed over to the other treatment after a 2-day washout period. Blood samples were obtained before and 1, 2, 4, 8, and 12 hours after consumption of the HFHC breakfast. The primary study outcomes were changes in area under the concentration-time curve (AUC) for interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). The secondary outcomes were safety and tolerability of lyophilized BRB powder. The chronology and values of measured serum concentrations for IL-6, TNF-α, and CRP were consistent with those described previously by other investigators. The AUC of serum IL-6 was lowered significantly (P = 0.03, n = 10) with BRB consumption (34.3 ± 7.6 pg·mL⁻¹·h⁻¹ compared with 42.4 ± 17.9 pg·mL⁻¹·h⁻¹ for consumption of the HFHC meal alone). However, no significant differences (change in AUC) were calculated for serum CRP and TNF-α. The findings of this pilot study suggest that consumption of lyophilized BRBs may attenuate postprandial inflammation in overweight or obese males consuming a HFHC meal. Further investigation of BRBs is warranted to better elucidate their inflammomodulatory potential.

  20. Single-agent erlotinib versus oral etoposide in patients with recurrent or refractory pediatric ependymoma: a randomized open-label study.

    PubMed

    Jakacki, Regina I; Foley, Margaret A; Horan, Julie; Wang, Jiuzhou; Kieran, Mark W; Bowers, Daniel C; Bouffet, Eric; Zacharoulis, Stergios; Gill, Stan C

    2016-08-01

    Overexpression of human epidermal growth factor receptor (HER/EGFR) is associated with various tumors, including ependymomas. To investigate whether EGFR inhibition was of benefit in pediatric patients with recurrent ependymoma, a multi-center, randomized, open-label, phase 2 study of oral erlotinib versus oral etoposide was undertaken. Twenty-five patients were randomized to receive erlotinib 85 mg/m(2) daily or etoposide 50 mg/m(2)/day for 21 consecutive days followed by a 7-day rest period. Courses were repeated every 28 days. In the erlotinib arm, no patient achieved a complete, partial, or minor response, and only 2 (15.4 %) patients showed stable disease as their best response. In the etoposide arm, 2 patients (16.7 %) demonstrated partial responses, 1 (8.3 %) patient demonstrated a minor response, and 2 (16.7 %) showed prolonged stable disease, for a prolonged disease control rate of 41.7 %. Three patients received at least nine cycles of etoposide (range 9-24 cycles) before discontinuing at the request of the physician and/or family. Four patients who failed etoposide in this study received erlotinib in a companion single arm study; none had a response. The futility criteria were met at the second interim analysis, and both studies were discontinued. Pharmacokinetics of erlotinib were similar to previous observations in pediatric patients. Overall, erlotinib was well tolerated and safety was consistent with its established profile in adults. The overall risk-benefit profile does not support the use of erlotinib in pediatric patients with recurrent ependymoma, whereas single-agent etoposide appears to have efficacy in a subset of patients. PMID:27287856

  1. Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation.

    PubMed

    Stoffregen, Clemens C; Odin, Elisabeth A; Carlsson, Göran U; Kurlberg, Göran K; Björkqvist, Hillevi G; Tångefjord, Maria T; Gustavsson, Bengt G

    2016-06-01

    The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study.

  2. Safety and Efficacy of Bupropion Extended Release in Treating a Community Sample of Hispanic and African American Adults With Major Depressive Disorder: An Open-Label Study

    PubMed Central

    Gross, Paul K.; Nourse, Rosemary; Wasser, Thomas E.; Bukenya, Deo

    2007-01-01

    Objectives: Many publications and federal agencies call for more trials and research on the effectiveness of medications and treatment needs in diverse patient populations with psychiatric disorders. This study investigates the effectiveness of bupropion extended release (XL) on a community sample of men and women of either Hispanic or African American heritage with major depressive disorder (MDD). Method: Twenty-six patients of Hispanic or African American descent with MDD as diagnosed by means of the Structured Clinical Interview for DSM-IV Axis I Disorders were required to have a score of 20 or greater on the Hamilton Rating Scale for Depression (17-item) (HAM-D-17) at baseline and prior to randomization. Patients were also required to have a score of 4 or greater on the Clinical Global Impressions-Severity of Illness scale (CGI-S) at baseline and prior to initiation of treatment. Patients were treated openly for an optimum of 9 weeks. Bupropion XL was initiated at 150 mg daily and then increased to 300 mg daily after 1 week and 450 mg daily 4 weeks later if judged clinically necessary by the investigator. Tools utilized for repeated-measures methodology indicating efficacy were the HAM-D-17, CGI-S, Clinical Global Impressions-Improvement scale (CGI-I), Change in Sexual Functioning Questionnaire (CSFQ), and the 18-item Motivation and Energy Inventory. The study was conducted from February 9, 2005, to March 23, 2006. Results: Efficacy was demonstrated on the HAM-D-17, CGI-S, CGI-I, and CSFQ (p < .05). Mean times ranged from 50% symptom reduction in about 2 weeks to 90% symptom reduction in less than 2 months. Dry mouth, transient stomach discomfort, and headache were the most commonly reported side effects. Conclusions: Data from this 10-week open-label study suggest bupropion XL is an effective and well tolerated treatment for depressive symptoms in the moderately to markedly ill Hispanic and African American community. PMID:17607332

  3. Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

    PubMed Central

    Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

    2014-01-01

    Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal®, in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Daflon® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended. PMID:24948863

  4. Safety and tolerability of varenicline tartrate (Champix(®)/Chantix(®)) for smoking cessation in HIV-infected subjects: a pilot open-label study.

    PubMed

    Cui, Qu; Robinson, Linda; Elston, Dawn; Smaill, Fiona; Cohen, Jeffrey; Quan, Corinna; McFarland, Nancy; Thabane, Lehana; McIvor, Andrew; Zeidler, Johannes; Smieja, Marek

    2012-01-01

    The prevalence of smoking in HIV-infected subjects is high. As a smoking cessation aid, varenicline (Champix(®), Pfizer, Saint-Laurent, QC, Canada or Chantix(®), Pfizer, Mission, KS) has not been previously evaluated in HIV-infected smokers. In this multicenter pilot open label study, varenicline 1.0 mg was used twice daily for 12 weeks with dose titration in the first week. Adverse events (AEs) during the treatment period were recorded. Changes from baseline in laboratory tests, vital signs, daily cigarette consumption, nicotine dependence, and withdrawal were measured through week 24. Self-reported abstinence was validated by serum cotinine at week 12. We enrolled 36 subjects with a mean of 29 pack-years of smoking and a minimum of 4 cigarettes per day. All but 1 were male, 33 (92%) were white. The most frequently reported AEs were nausea (33%), abnormal dreams (31%), affect lability (19%), and insomnia (19%). Six (17%) subjects discontinued varenicline due to AEs. No grade 3/4 laboratory abnormalities or serious AEs occurred during the study. There was no significant change in HIV viral load. CD4 counts increased by 69 cells/mm3 (p = 0.001) at week 24. Serum cotinine-verified 4-week continuous abstinence rate through weeks 9-12 was 42% (95% confidence interval [CI]: 26-58%). AEs and abstinence rates were comparable to those in published randomized controlled trials conducted in generally healthy HIV-negative smokers. Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common. The most common AE was nausea, with no adverse effect on HIV treatment outcome. Close monitoring of liver enzymes and blood pressure is recommended for HIV-positive smokers taking varenicline.

  5. Phase I, Open-Label, Single-Dose Study To Evaluate the Pharmacokinetics and Safety of Telbivudine in Children and Adolescents with Chronic Hepatitis B

    PubMed Central

    Ke, June; Uy, Grace; Bosheva, Miroslava; Qi, Yin; Praestgaard, Jens

    2013-01-01

    Telbivudine is a nucleoside analogue that has been approved for the treatment of chronic hepatitis B virus (HBV) infection in adults at 600 mg/day. We conducted a phase I, open-label, first-in-pediatrics study to investigate the safety and pharmacokinetics of a single dose of telbivudine in HBV-infected children and adolescents. Eligible patients were enrolled sequentially from older to younger groups, with evaluation of safety and available pharmacokinetic data after each stratum. Adolescent patients (>12 to 18 years) received a single dose of 600 mg telbivudine as an oral solution, while children aged 2 to 12 years received a single dose of 15 or 25 mg/kg of body weight up to a maximum of 600 mg. Telbivudine was well tolerated; all adverse events were mild, and none occurred in more than one patient. The plasma telbivudine concentration-versus-time profiles in adolescents given 600 mg were similar to the mean profile of healthy adults receiving the same oral dose. Children aged 2 to <6 and 6 to 12 years receiving a single 15-mg/kg dose showed similar plasma exposures. To predict the steady-state exposure, plasma concentration-versus-time profiles for patients aged 2 to 12 years (15 mg/kg) and >12 to 18 years (600 mg) were fitted to a two-compartment 1st-order, microconstant, lag time, 1st-order elimination pharmacokinetic (PK) model. This analysis predicted the following dosages to mimic exposures in healthy adults receiving 600 mg/day: 20 mg/kg/day for children 2 to 12 years and 600 mg/day for adolescents. Studies are ongoing to evaluate the efficacy of the recommended dose in pediatric patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00907894.) PMID:23774433

  6. Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study.

    PubMed

    Arima, Hiroshi; Oiso, Yutaka; Juul, Kristian Vinter; Nørgaard, Jens Peter

    2013-01-01

    Central diabetes insipidus (CDI) is associated with arginine vasopressin (AVP) deficiency with resultant polyuria and polydipsia. Intranasal desmopressin provides physiological replacement but oral formulations are preferred for their ease of administration. This study aimed to demonstrate the efficacy and safety of desmopressin orally disintegrating tablet (ODT) in the treatment of Japanese patients with CDI, and confirm that antidiuresis is maintained on switching from intranasal desmopressin to desmopressin ODT. A total of 20 patients aged 6-75 years with CDI were included in this 4-week multicenter, open-label study. Following observation, patients switched from intranasal desmopressin to desmopressin ODT with titration to optimal dose over ≤5 days at the study site. Following three consecutive doses with stable patient fluid balance, patients were discharged with visits at Weeks 2 and 4. Following titration from intranasal desmopressin to ODT, the mean 24-hour urine volume was unchanged, indicating similar antidiuresis with both formulations. The proportion of patients with endpoint measurements (urine osmolality, 24-hour urine volume, hourly diuresis rate and urine-specific gravity) within normal range at Days 1-2 (intranasal desmopressin) and Week 4 (desmopressin ODT) was similar. The mean daily dose ratio of intranasal desmopressin to desmopressin ODT (Week 4) was 1:24 but a wide range was observed across individuals to maintain adequate antidiuretic effect. Hyponatraemia was generally mild and managed by dose titration. Desmopressin ODT achieved sufficient antidiuretic control compared to intranasal therapy and was well tolerated over long-term treatment. The wide range of intranasal:ODT dose ratios underline the importance of individual titration. PMID:23811987

  7. Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study.

    PubMed

    Arima, Hiroshi; Oiso, Yutaka; Juul, Kristian Vinter; Nørgaard, Jens Peter

    2013-01-01

    Central diabetes insipidus (CDI) is associated with arginine vasopressin (AVP) deficiency with resultant polyuria and polydipsia. Intranasal desmopressin provides physiological replacement but oral formulations are preferred for their ease of administration. This study aimed to demonstrate the efficacy and safety of desmopressin orally disintegrating tablet (ODT) in the treatment of Japanese patients with CDI, and confirm that antidiuresis is maintained on switching from intranasal desmopressin to desmopressin ODT. A total of 20 patients aged 6-75 years with CDI were included in this 4-week multicenter, open-label study. Following observation, patients switched from intranasal desmopressin to desmopressin ODT with titration to optimal dose over ≤5 days at the study site. Following three consecutive doses with stable patient fluid balance, patients were discharged with visits at Weeks 2 and 4. Following titration from intranasal desmopressin to ODT, the mean 24-hour urine volume was unchanged, indicating similar antidiuresis with both formulations. The proportion of patients with endpoint measurements (urine osmolality, 24-hour urine volume, hourly diuresis rate and urine-specific gravity) within normal range at Days 1-2 (intranasal desmopressin) and Week 4 (desmopressin ODT) was similar. The mean daily dose ratio of intranasal desmopressin to desmopressin ODT (Week 4) was 1:24 but a wide range was observed across individuals to maintain adequate antidiuretic effect. Hyponatraemia was generally mild and managed by dose titration. Desmopressin ODT achieved sufficient antidiuretic control compared to intranasal therapy and was well tolerated over long-term treatment. The wide range of intranasal:ODT dose ratios underline the importance of individual titration.

  8. Symptomatic or prophylactic treatment of weekend migraine: an open-label, nonrandomized, comparison study of frovatriptan versus naproxen sodium versus no therapy

    PubMed Central

    Guidotti, Mario; Barrilà, Caterina; Leva, Serena; De Piazza, Claudio; Omboni, Stefano

    2013-01-01

    Background Migraine often occurs during weekends. The efficacy of frovatriptan, naproxen sodium, or no therapy for the acute or prophylactic treatment of weekend migraineurs was tested in an open-label, nonrandomized pilot study. Methods Twenty-eight subjects (mean age 36 ± 12 years, including 18 females) suffering from migraine without aura were followed up for six consecutive weekends. No treatment was administered during the first two weekends. On the third and fourth weekends, patients were given frovatriptan 2.5 mg and on the fifth and sixth weekends naproxen sodium 500 mg. Treatment was taken on Saturday and Sunday morning, regardless of the occurrence of migraine. Efficacy was evaluated through a diary, where patients reported the severity of migraine on a scale from 0 (no migraine) to 10 (severe migraine) and use of rescue medication. Results The migraine severity score was significantly lower with frovatriptan (4.8 [95% confidence interval (CI) 3.8–5.9]) than with naproxen sodium (5.7 [CI 5.1–6.4], P< 0.05 versus frovatriptan) or no therapy (6.6 [6.2–7.0], P< 0.01 versus frovatriptan). The difference in favor of frovatriptan was more striking in patients not taking rescue medication (frovatriptan, 1.9 [1.5–2.3]) versus naproxen sodium 3.6 [3.0–4.2], P< 0.001) and versus no therapy (5.1 [4.4–5.8], P< 0.001) and on the second day of treatment. The rate of use of rescue medication was significantly (P< 0.05) lower on frovatriptan (12.5%) than on naproxen sodium (31.3%) or no therapy (56.3%). Conclusion This pilot study provides the first evidence of the efficacy of a second-generation triptan as symptomatic or prophylactic treatment for weekend migraine. PMID:23355779

  9. Evaluation of Biomarkers of Exposure in Smokers Switching to a Carbon-Heated Tobacco Product: A Controlled, Randomized, Open-Label 5-Day Exposure Study

    PubMed Central

    Haziza, Christelle; Weitkunat, Rolf; Magnette, John

    2016-01-01

    Introduction: Tobacco harm reduction aims to provide reduced risk alternatives to adult smokers who would otherwise continue smoking combustible cigarettes (CCs). This randomized, open-label, three-arm, parallel-group, single-center, short-term confinement study aimed to investigate the effects of exposure to selected harmful and potentially harmful constituents (HPHCs) of cigarette smoke in adult smokers who switched to a carbon-heated tobacco product (CHTP) compared with adult smokers who continued to smoke CCs and those who abstained from smoking for 5 days. Methods: Biomarkers of exposure to HPHCs, including nicotine and urinary excretion of mutagenic material, were measured in 24-hour urine and blood samples in 112 male and female Caucasian smokers switching from CCs to the CHTP ad libitum use. Puffing topography was assessed during product use. Results: Switching to the CHTP or smoking abstinence (SA) resulted in marked decreases from baseline to Day 5 in all biomarkers of exposure measured, including carboxyhemoglobin (43% and 55% decrease in the CHTP and SA groups, respectively). The urinary excretion of mutagenic material was also markedly decreased on Day 5 compared with baseline (89% and 87% decrease in the CHTP and SA groups, respectively). No changes in biomarkers of exposure to HPHCs or urinary mutagenic material were observed between baseline and Day 5 in the CC group. Conclusions: Our results provide clear evidence supporting a reduction in the level of exposure to HPHCs of tobacco smoke in smokers who switch to CHTP under controlled conditions, similar to that observed in SA. Implications: The reductions observed in biomarkers of exposure to HPHCs of tobacco smoke in this short-term study could potentially also reduce the incidence of cancer, cardiovascular and respiratory diseases in those smokers who switch to a heated tobacco product. PMID:26817490

  10. A Randomized, Open-Label, Comparative Study of Efficacy and Safety of Tolterodine Combined with Tamsulosin or Doxazosin in Patients with Benign Prostatic Hyperplasia

    PubMed Central

    Cao, Yanwei; Wang, Yonghua; Guo, Lei; Yang, Xuecheng; Chen, Tao; Niu, Haitao

    2016-01-01

    Background Benign prostatic hyperplasia (BPH), a common disease in men over age 50 years, often causes bladder outlet obstruction and lower urinary tract symptoms (LUTS). Alpha blockers in combination with muscarinic receptor antagonists may have the potential to improve symptoms. This study aimed to assess the efficacy and safety of doxazosin or tamsulosin combined with tolterodine extend release (ER) in patients with BPH and LUTS. Material/Methods In a prospective, randomized, open-label study (ChiCTR-IPR-15005763), 220 consecutive men with BPH and LUTS were allocated to receive doxazosin 4 mg and tolterodine ER 4 mg per day (doxazosin group) or tamsulosin 0.2 mg and tolterodine ER 4 mg per day (tamsulosin group). Treatment lasted 12 weeks. The primary endpoint was the international prostatic symptom score (IPSS). Secondary endpoints were quality of life (QoL) and maximum flow rate (Qmax), which were evaluated at 0, 6, and 12 weeks, and urodynamic parameters assessed at 0 and 12 weeks. Results A total of 192 patients completed the trial. Baseline measurements showed no differences between the groups. After 6 weeks, IPSS improved in both groups and QoL was significantly better in the doxazosin group (P=0.01). After 12 weeks, Qmax, IPSS, QoL, intravesical pressure (Pves), and bladder compliance (BC) in the doxazosin group were significantly better than in the tamsulosin group (P=0.03, P<0.001, P<0.001, P=0.027, and P=0.044, respectively). Conclusions Administration of alpha blockers combined with muscarinic receptor blocker for 12 weeks improved LUTS in men with BPH. PMID:27260129

  11. A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease

    PubMed Central

    Friedman, Neil J; Butron, Karla; Robledo, Nora; Loudin, James; Baba, Stephanie N; Chayet, Arturo

    2016-01-01

    Background Dry eye disease (DED), a chronic disorder affecting the tear film and lacrimal functional unit, is a widely prevalent condition associated with significant burden and unmet treatment needs. Since specific neural circuits play an important role in maintaining ocular surface health, microelectrical stimulation of these pathways could present a promising new approach to treating DED. This study evaluated the efficacy and safety of nasal electrical stimulation in patients with DED. Methods This prospective, open-label, single-arm, nonrandomized pilot study included 40 patients with mild to severe DED. After undergoing two screening visits, enrolled subjects were provided with a nasal stimulation device and instructed to use it at home four times daily (or more often as needed). Follow-up assessments were conducted up to day 180. The primary efficacy endpoint was the difference between unstimulated and stimulated tear production quantified by Schirmer scores. Additional efficacy endpoints included change from baseline in corneal and conjunctival staining, symptoms evaluated on a Visual Analog Scale, and Ocular Surface Disease Index scores. Safety parameters included adverse event (AE) rates, visual acuity, intraocular pressure, slit-lamp biomicroscopy, indirect ophthalmoscopy, and endoscopic nasal examinations. Results Mean stimulated Schirmer scores were significantly higher than the unstimulated scores at all visits, and corneal and conjunctival staining and symptom scores from baseline to day 180 were significantly reduced. No serious device-related AEs and nine nonserious AEs (three device-related) were reported. Intraocular pressure remained stable and most subjects showed little or no change in visual acuity at days 30 and 180. No significant findings from other clinical examinations were noted. Conclusion Neurostimulation of the nasolacrimal pathway is a safe and effective means of increasing tear production and reducing symptoms of dry eye in patients

  12. A Randomized, Open-Label, Comparative Study of Efficacy and Safety of Tolterodine Combined with Tamsulosin or Doxazosin in Patients with Benign Prostatic Hyperplasia.

    PubMed

    Cao, Yanwei; Wang, Yonghua; Guo, Lei; Yang, Xuecheng; Chen, Tao; Niu, Haitao

    2016-01-01

    BACKGROUND Benign prostatic hyperplasia (BPH), a common disease in men over age 50 years, often causes bladder outlet obstruction and lower urinary tract symptoms (LUTS). Alpha blockers in combination with muscarinic receptor antagonists may have the potential to improve symptoms. This study aimed to assess the efficacy and safety of doxazosin or tamsulosin combined with tolterodine extend release (ER) in patients with BPH and LUTS. MATERIAL AND METHODS In a prospective, randomized, open-label study (ChiCTR-IPR-15005763), 220 consecutive men with BPH and LUTS were allocated to receive doxazosin 4 mg and tolterodine ER 4 mg per day (doxazosin group) or tamsulosin 0.2 mg and tolterodine ER 4 mg per day (tamsulosin group). Treatment lasted 12 weeks. The primary endpoint was the international prostatic symptom score (IPSS). Secondary endpoints were quality of life (QoL) and maximum flow rate (Qmax), which were evaluated at 0, 6, and 12 weeks, and urodynamic parameters assessed at 0 and 12 weeks. RESULTS A total of 192 patients completed the trial. Baseline measurements showed no differences between the groups. After 6 weeks, IPSS improved in both groups and QoL was significantly better in the doxazosin group (P=0.01). After 12 weeks, Qmax, IPSS, QoL, intravesical pressure (Pves), and bladder compliance (BC) in the doxazosin group were significantly better than in the tamsulosin group (P=0.03, P<0.001, P<0.001, P=0.027, and P=0.044, respectively). CONCLUSIONS Administration of alpha blockers combined with muscarinic receptor blocker for 12 weeks improved LUTS in men with BPH.

  13. Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study.

    PubMed

    Chopra, Arvind; Chandrashekara, S; Iyer, Rajgopalan; Rajasekhar, Liza; Shetty, Naresh; Veeravalli, Sarathchandra Mouli; Ghosh, Alakendu; Merchant, Mrugank; Oak, Jyotsna; Londhey, Vikram; Barve, Abhijit; Ramakrishnan, M S; Montero, Enrique

    2016-04-01

    The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period. (Clinical Trial Registry of India, http://ctri.nic.in/Clinicaltrials/login.php , CTRI/2008/091/000295).

  14. Safety and Immunogenicity of Pfs25-EPA/Alhydrogel®, a Transmission Blocking Vaccine against Plasmodium falciparum: An Open Label Study in Malaria Naïve Adults

    PubMed Central

    Talaat, Kawsar R.; Ellis, Ruth D.; Hurd, Janet; Hentrich, Autumn; Gabriel, Erin; Hynes, Noreen A.; Rausch, Kelly M.; Zhu, Daming; Muratova, Olga; Herrera, Raul; Anderson, Charles; Jones, David; Aebig, Joan; Brockley, Sarah; MacDonald, Nicholas J.; Wang, Xiaowei; Fay, Michael P.; Healy, Sara A.; Durbin, Anna P.; Narum, David L.; Wu, Yimin; Duffy, Patrick E.

    2016-01-01

    Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel® in a malaria-endemic population. PMID:27749907

  15. An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain

    PubMed Central

    Onouchi, Kenji; Koga, Hiroaki; Yokoyama, Kazumasa; Yoshiyama, Tamotsu

    2014-01-01

    Purpose Studies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4–17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure. Patients and methods This was a 53-week, multicenter, open-label trial of pregabalin (150–600 mg/day) in Japanese patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke. Results A total of 103 patients received pregabalin (post-stroke =60; spinal cord injury =38; and multiple sclerosis =5). A majority of patients (87.4%) experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1%) or moderate (9.2%) in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS), and present pain intensity scores on the Short-Form McGill Pain Questionnaire (SF-MPQ) and ten-item modified Brief Pain Inventory (mBPI-10) total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were −20.1 and −1.4, respectively. Conclusion These findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in patients with chronic central neuropathic pain. PMID:25114584

  16. Adding Memantine to Rivastigmine Therapy in Patients With Mild-to-Moderate Alzheimer's Disease: Results of a 12-Week, Open-Label Pilot Study

    PubMed Central

    Riepe, Matthias W.; Adler, Georg; Ibach, Bernd; Weinkauf, Birgit; Gunay, Ibrahim; Tracik, Ferenc

    2006-01-01

    Objective: At present, inhibition of cholines-terase is the treatment of choice for subjects with mild-to-moderate Alzheimer's disease (AD). Memantine, a noncompetitive antagonist at N-methyl-d-aspartate receptors, is currently used to treat subjects with moderate-to-severe AD. The goal of this multicenter, open-label pilot study was to investigate whether combination therapy with memantine added to rivastigmine is safe and beneficial in subjects with mild-to-moderate AD. Method: Patients with a DSM-IV diagnosis of dementia of the Alzheimer's type (N = 95), who were treated with rivastigmine (6–12 mg/day) for a maximum duration of 24 weeks prior to baseline, received memantine (5–20 mg/day) in combination with rivastigmine for 12 weeks. The primary efficacy variable was the change in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score at the end of 12 weeks compared with baseline. The study was conducted between September 15, 2003, and May 27, 2004. Results: There was a statistically significant difference between baseline and week 12 for the ADAS-cog total score, showing a positive effect of combination therapy. Combination therapy did not evidence any unexpected safety concerns and was well-tolerated by most patients. Conclusion: Memantine in combination with rivastigmine appears to be safe and beneficial in patients with mild-to-moderate AD. Our results need to be confirmed in a large, long-term, randomized, double-blind, placebo-controlled clinical trial. PMID:17235381

  17. No Evidence of Harms of Probiotic Lactobacillus rhamnosus GG ATCC 53103 in Healthy Elderly—A Phase I Open Label Study to Assess Safety, Tolerability and Cytokine Responses

    PubMed Central

    Hibberd, Patricia L.; Kleimola, Lauren; Fiorino, Anne-Maria; Botelho, Christine; Haverkamp, Miriam; Andreyeva, Irina; Poutsiaka, Debra; Fraser, Claire; Solano-Aguilar, Gloria; Snydman, David R.

    2014-01-01

    Background Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly. Objectives The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU) of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines. Methods Fifteen elderly volunteers, aged 66–80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions. Results There were no serious adverse events. The 15 volunteers had a total of 47 events (range 1–7 per volunteer), 39 (83%) of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70%) of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea), 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038) while there was no difference in other pro- or anti-inflammatory plasma cytokines. Conclusions Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older. Trial Registration ClinicalTrials.gov NCT 01274598 PMID:25438151

  18. Evaluation of miglustat as maintenance therapy after enzyme therapy in adults with stable type 1 Gaucher disease: a prospective, open-label non-inferiority study

    PubMed Central

    2012-01-01

    Background Previous studies have provided equivocal data on the use of miglustat as maintenance therapy in Gaucher disease type 1. We report findings from a clinical trial evaluating the effects of miglustat treatment in patients with stable type 1 Gaucher disease after enzyme therapy. Methods Adult type 1 Gaucher disease patients stabilized during at least 3 years of previous enzyme therapy were included in this 2-year, prospective, open-label non-inferiority study. The primary endpoint was percent change from baseline in liver volume. Secondary endpoints included changes in spleen volume, hemoglobin concentration and platelet count. Results Forty-two patients were enrolled (mean±SD age, 45.1±12.7 years; previous enzyme therapy duration 9.5±4.0 years). Median (range) exposure to miglustat 100 mg t.i.d. was 658 (3–765) days. Twenty-one patients discontinued treatment prematurely; 13 due to adverse events, principally gastrointestinal. The upper 95% confidence limit of mean percent change in liver volume from baseline to end of treatment was below the non-inferiority margin of 10% (–1.1%; 95%CI −6.0, 3.9%). Mean (95%CI) changes in spleen volume, hemoglobin concentration and platelet count were 102 (24,180) mL, –0.95 (−1.38, –0.53) g/dL and −44.1 (–57.6, –30.7) ×109/L, respectively. Conclusions The primary efficacy endpoint was met; overall there was no change in liver volume during 24 months of miglustat therapy. Several patients showed a gradual deterioration in some disease manifestations, suggesting that miglustat could maintain clinical stability, but not in all patients. Miglustat demonstrated a predictable profile of safety and tolerability that was consistent with that reported in previous clinical trials and experience in clinical practice. Trial registration Clinicaltrials.gov identifier NCT00319046 PMID:23270487

  19. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study

    PubMed Central

    Douillard, J-Y; Ostoros, G; Cobo, M; Ciuleanu, T; McCormack, R; Webster, A; Milenkova, T

    2014-01-01

    Background: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Methods: Treatment: gefitinib 250 mg day−1 until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. Results: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8% adenocarcinoma 97.2% never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5–77.7), DCR 90.6% (95% CI 83.5–94.8), median PFS 9.7 months (95% CI 8.5–11.0), median OS 19.2 months (95% CI 17.0–NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15% SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8–74.7). Conclusion: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable. PMID:24263064

  20. Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study

    PubMed Central

    2013-01-01

    Background Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. Methods This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Results Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Conclusion Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. Trial registration ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18. PMID:24053191

  1. Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

    PubMed Central

    Hashimoto, Tasuku; Sakurai, Daiji; Oda, Yasunori; Hasegawa, Tadashi; Kanahara, Nobuhisa; Sasaki, Tsuyoshi; Komatsu, Hideki; Takahashi, Junpei; Oiwa, Takahiro; Sekine, Yoshimoto; Watanabe, Hiroyuki; Iyo, Masaomi

    2015-01-01

    Background We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood. Methods We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a ≥50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs), moderate-to-severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines. Results Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10). Baseline serum levels of interleukin-6 (Z=−2.155; P=0.031) and interleukin-8 (Z=−2.616; P=0.009) were significantly higher when moderate-to-severe AEs were present (n=13 patients with moderate-to-severe AEs). Serum levels of macrophage inflammatory protein-1β showed a significant continuous decrease from the baseline level (Friedman’s test: χ2=23.9, df=4, P<0.001) only in non-responders. Conclusion These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1β as potential blood biomarkers could be utilized to identify the responsiveness of patients to serotonin and norepinephrine reuptake inhibitor like milnacipran, or to identify those patients who may experience AEs strong enough to warrant discontinuation of treatment. PMID:26677330

  2. Duloxetine and care management treatment of older adults with comorbid major depressive disorder and chronic low back pain: results of an open-label pilot study

    PubMed Central

    Karp, Jordan F.; Weiner, Debra K.; Dew, Mary A.; Begley, Amy; Miller, Mark D.; Reynolds, Charles F.

    2010-01-01

    Objective: In older adults, major depressive disorder (MDD) and chronic low back pain (CLBP) are common and mutually exacerbating. We predicted that duloxetine pharmacotherapy and Depression and Pain Care Management (DPCM) would result in (1) significant improvement in MDD and CLBP and (2) significant improvements in health-related quality of life, anxiety, disability, self-efficacy, and sleep quality. Design and Intervention: Twelve week open-label study using duloxetine up to 120 mg/day + DPCM. Setting: Outpatient late-life depression research clinic. Patients: Thirty community-dwelling adults >60 years old. Outcome Measures: Montgomery Asberg Depression Rating Scale (MADRS) and McGill Pain Questionnaire-Short Form (MPQ-SF). Results: 46.7% (n = 14) of the sample had a depression remission. All subjects who met criteria for the depression remission also had a pain response. 93.3% (n = 28) had a significant pain response. Of the subjects who met criteria for a low back pain response, 50% (n = 14) also met criteria for the depression remission. The mean time to depression remission was 7.6 (SE = 0.6) weeks. The mean time to pain response was 2.8 (SE = 0.5) weeks. There were significant improvements in mental health-related quality of life, anxiety, sleep quality, somatic complaints, and both self-efficacy for pain management and for coping with symptoms. Physical health-related quality of life, back pain-related disability, and self-efficacy for physical functioning did not improve. Conclusions: Serotonin and norepinephrine reuptake inhibitors like duloxetine delivered with DPCM may be a good choice to treat these linked conditions in older adults. Treatments that target low self-efficacy for physical function and improving disability may further increase response rates. PMID:19750557

  3. Study protocol for a randomized controlled trial to assess the feasibility of an open label intervention to improve hydroxyurea adherence in youth with sickle cell disease

    PubMed Central

    Smaldone, Arlene; Findley, Sally; Bakken, Suzanne; Matiz, L. Adriana; Rosenthal, Susan L.; Jia, Haomiao; Matos, Sergio; Manwani, Deepa; Green, Nancy S.

    2016-01-01

    Background Community health workers (CHW) are increasingly recognized as a strategy to improve health outcomes for the underserved with chronic diseases but has not been formally explored in adolescents with sickle cell disease (SCD). SCD primarily affects African American, Hispanic and other traditionally underserved populations. Hydroxyurea (HU), an oral, once-daily medication, is the only approved therapeutic drug for sickle cell disease and markedly reduces symptoms, morbidity and mortality and improves quality of life largely by increasing hemoglobin F blood levels. This paper presents the rationale, study design and protocol for an open label randomized controlled trial to improve parent-youth partnerships in self-management and medication adherence to HU in adolescents with SCD. Methods/Design A CHW intervention augmented by text messaging was designed for adolescents with SCD ages 10–18 years and their parents to improve daily HU adherence. Thirty adolescent parent dyads will be randomized with 2:1 intervention group allocation. Intervention dyads will establish a relationship with a culturally aligned CHW to identify barriers to HU use, identify cues to build a habit, and develop a dyad partnership to improve daily HU adherence and achieve their individualized “personal best” hemoglobin F target. Intervention feasibility, acceptability and efficacy will be assessed via a 2-site trial. Outcomes of interest are HU adherence, dyad self-management communication, quality of life, and resource use. Discussion Despite known benefits, poor HU adherence is common. If feasible and acceptable, the proposed intervention may improve health of underserved adolescents with SCD by enhancing long-term HU adherence. PMID:27327779

  4. Pulmonary toxicity of cyclophosphamide: a 1-year study

    SciTech Connect

    Morse, C.C.; Sigler, C.; Lock, S.; Hakkinen, P.J.; Haschek, W.M.; Witschi, H.P.

    1985-01-01

    The development of cyclophosphamide-induced pulmonary lesions over a 1-year period was studied in mice. Male BALB/c mice received a single intraperitoneal injection of 100 mg/kg of cyclophosphamide. Within 3 weeks there were scattered foci of intraalveolar foamy macrophages. With time, these foci increased in size and, 1 year later, occupied large areas in all lung lobes. There was also diffuse interstitial fibrosis. Chemical determination done 3, 12, 24, and 52 weeks after cyclophosphamide showed that lungs of animals treated with cyclophosphamide had significantly more hydroxyproline per lung than controls. One year after cyclophosphamide pressure - volume curves measured in vivo were shifted down and to the right and total lung volumes were decreased. A single injection of cyclophosphamide produced an irreversible and progressive pulmonary lesion. 16 references, 5 figures, 3 tables.

  5. Efficacy and tolerability of carbamazepine for the treatment of painful diabetic neuropathy in adults: a 12-week, open-label, multicenter study

    PubMed Central

    Saeed, Tariq; Nasrullah, Muhammad; Ghafoor, Adnan; Shahid, Riaz; Islam, Nadeem; Khattak, Mohammad Usman; Maheshwary, Neeta; Siddiqi, Ahson; Khan, Muhammad Athar

    2014-01-01

    Objective Anticonvulsants are increasingly being used in the symptomatic management of several neuropathic pain disorders. The present observational study was designed to evaluate the efficacy, tolerability, and quality of life (QoL) of carbamazepine use for 12 weeks in patients with painful diabetic neuropathy, in Pakistan. Methods This was a 12-week, multicenter, open-label, uncontrolled trial in adult type 2 diabetic patients (aged 18–65 years) suffering from clinically confirmed neuropathic pain (Douleur Neuropathique en 4 [DN4] score ≥4). Change in neuropathic pain at week 12 compared with baseline was assessed using the Brief Pain Inventory Scale–Short Form (pain severity score and pain interference score). QoL was determined by the American Chronic Pain Association QoL scale. Safety was assessed based on patient reported adverse events (AEs) and serious AEs. Results Of the total 500 screened patients, 452 enrolled and completed the study. The mean (± standard deviation [SD]) pain interference score decreased from 4.5±2.0 at baseline to 3.1±1.9 at week 12 (P<0.001). The mean (± SD) pain severity score decreased from 5.8±2.0 at baseline to 3.6±2.2 at week 12 (P<0.001). There was a decrease of ≥30% in the pain severity score between visits. The mean (± SD) QoL scale score improved from 5.9±1.6 at baseline to 8.0±1.7 at week 12. A total of ten (2.2%) patients reported AEs during the study period. No patient discontinued the study due to AEs. Conclusion In this real-life experience study, carbamazepine, when prescribed for 12 weeks to adult diabetic patients suffering from neuropathic pain, showed pain-relief effect, with reduced mean pain severity and mean pain interference scores and with improved QoL and good tolerability profile. PMID:25061334

  6. A Prospective, Multicentre, Open-Label Single-Arm Exploratory Study to Evaluate Efficacy and Safety of Saroglitazar on Hypertriglyceridemia in HIV Associated Lipodystrophy

    PubMed Central

    Joshi, Shashank

    2016-01-01

    Objective This study was designed to explore the efficacy and safety of saroglitazar 4 mg on hypertriglyceridemia in patients with HIV associated lipodystrophy. Methods During this 12-week prospective, multi-centric, open-label, single arm exploratory study, 50 patients were enrolled to receive saroglitazar 4 mg orally once daily in the morning before breakfast. The primary efficacy endpoint was the percent change in triglyceride (TG) levels from baseline to Week 6 and Week 12. The secondary efficacy endpoints were assessment of low-density-lipoprotein (LDL), very-low-density-lipoprotein (VLDL), high-density-lipoprotein (HDL), non-HDL cholesterol, total cholesterol, apo-lipoprotein (Apo) A1, Apo B, and C-peptide and fasting insulin for HOMA beta and HOMA IR. Safety assessment was performed during the study. Results Saroglitazar 4 mg significantly decreased the serum TG levels from baseline at Week 6 (percent change: -40.98; 95% CI: -50.82, -31.15) and Week 12 (percent change -45.11; 95% CI: -52.37, -37.86). Reduction in VLDL cholesterol (percent change: -46.33; 95% CI: -52.89, -39.76) and total cholesterol (percent change: 7.37; 95% CI: 1.96, 12.78) was observed at week 12 from baseline. Saroglitazar increased HDL cholesterol (percent change: 34.56, 95% CI: 22.22, 46.90), Apo A1 (percent change: 33.16; 95% CI: 18.69, 47.63) and Apo B (percent change: 10.55, 95% CI: 2.86, 18.25) levels at week 12 from baseline. Saroglitazar treatment led to increase in the C-peptide (percent change: 59.42, 95% CI: 48.78, 70.06), fasting insulin levels (percent change: 47.10; 95% CI: 38.63, 55.57), HOMA of beta cell function for C-peptide (percent change: 71.67; 95% CI: 39.09, 104.26) and HOMA of insulin resistance for C-peptide (percent change: 58.29, 95% CI: 46.74, 69.83) at week 12 from baseline. Saroglitazar treatment was safe and well tolerated in this study. Conclusion Overall, the observed changes in lipid profile after 12 weeks of saroglitazar treatment were in the direction

  7. Open-label, single-dose, parallel-group study in healthy volunteers to determine the drug-drug interaction potential between KAE609 (cipargamin) and piperaquine.

    PubMed

    Stein, Daniel S; Jain, Jay Prakash; Kangas, Michael; Lefèvre, Gilbert; Machineni, Surendra; Griffin, Paul; Lickliter, Jason

    2015-01-01

    KAE609 represents a new class of potent, fast-acting, schizonticidal antimalarials. This study investigated the safety and pharmacokinetics of KAE609 in combination with the long-acting antimalarial piperaquine (PPQ) in healthy volunteers. A two-way pharmacokinetic interaction was hypothesized for KAE609 and PPQ, as both drugs are CYP3A4 substrates and inhibitors. The potential for both agents to affect the QT interval was also assessed. This was an open-label, parallel-group, single-dose study with healthy volunteers. Subjects were randomized to four parallel dosing arms with five cohorts (2:2:2:2:1), receiving 75 mg KAE609 plus 320 mg PPQ, 25 mg KAE609 plus 1,280 mg PPQ, 25 mg KAE609 alone, 320 mg PPQ alone, or 1,280 mg PPQ alone. Triplicate electrocardiograms were performed over the first 24 h after dosing, with single electrocardiograms at other time points. Routine safety (up to 89 days) and pharmacokinetic (up to 61 days) assessments were performed. Of the 110 subjects recruited, 99 completed the study. Coadministration of PPQ had no overall effect on exposure to KAE609, although 1,280 mg PPQ decreased the KAE609 maximum concentration (Cmax) by 17%. The group that received 25 mg KAE609 plus 1,280 mg PPQ showed a 32% increase in the PPQ area under the concentration-time curve from 0 to infinity (AUCinf), while the group that received 75 mg KAE609 plus 320 mg PPQ showed a 14% reduction. Mean changes from baseline in the QT interval corrected by Fridericia's method (QTcF) and the QT interval corrected by Bazett's method (QTcB) with PPQ were consistent with its known effects. PPQ but not KAE609 exposure correlated with corrected QT interval (QTc) increases, and KAE609 did not affect the PPQ exposure-QTc relationship. The QTcF effect for PPQ (least-squares estimate of the difference in mean maximal changes from baseline of 7.47 ms [90% confidence interval, 3.55 to 11.4 ms]) was consistent with the criteria for a positive thorough QT study. No subject had QTcF or

  8. Open-Label, Single-Dose, Parallel-Group Study in Healthy Volunteers To Determine the Drug-Drug Interaction Potential between KAE609 (Cipargamin) and Piperaquine

    PubMed Central

    Jain, Jay Prakash; Kangas, Michael; Lefèvre, Gilbert; Machineni, Surendra; Griffin, Paul; Lickliter, Jason

    2015-01-01

    KAE609 represents a new class of potent, fast-acting, schizonticidal antimalarials. This study investigated the safety and pharmacokinetics of KAE609 in combination with the long-acting antimalarial piperaquine (PPQ) in healthy volunteers. A two-way pharmacokinetic interaction was hypothesized for KAE609 and PPQ, as both drugs are CYP3A4 substrates and inhibitors. The potential for both agents to affect the QT interval was also assessed. This was an open-label, parallel-group, single-dose study with healthy volunteers. Subjects were randomized to four parallel dosing arms with five cohorts (2:2:2:2:1), receiving 75 mg KAE609 plus 320 mg PPQ, 25 mg KAE609 plus 1,280 mg PPQ, 25 mg KAE609 alone, 320 mg PPQ alone, or 1,280 mg PPQ alone. Triplicate electrocardiograms were performed over the first 24 h after dosing, with single electrocardiograms at other time points. Routine safety (up to 89 days) and pharmacokinetic (up to 61 days) assessments were performed. Of the 110 subjects recruited, 99 completed the study. Coadministration of PPQ had no overall effect on exposure to KAE609, although 1,280 mg PPQ decreased the KAE609 maximum concentration (Cmax) by 17%. The group that received 25 mg KAE609 plus 1,280 mg PPQ showed a 32% increase in the PPQ area under the concentration-time curve from 0 to infinity (AUCinf), while the group that received 75 mg KAE609 plus 320 mg PPQ showed a 14% reduction. Mean changes from baseline in the QT interval corrected by Fridericia's method (QTcF) and the QT interval corrected by Bazett's method (QTcB) with PPQ were consistent with its known effects. PPQ but not KAE609 exposure correlated with corrected QT interval (QTc) increases, and KAE609 did not affect the PPQ exposure-QTc relationship. The QTcF effect for PPQ (least-squares estimate of the difference in mean maximal changes from baseline of 7.47 ms [90% confidence interval, 3.55 to 11.4 ms]) was consistent with the criteria for a positive thorough QT study. No subject had QTcF or

  9. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.

    PubMed

    Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

    2016-03-01

    The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder.

  10. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies

    PubMed Central

    Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

    2016-01-01

    The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5–20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5–20mg/day) was 4.5–7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5–20mg/day) were nausea (20.9–31.2%) and vomiting (2.9–6.5%). For vortioxetine (5–20mg/day), the incidence of TEAEs associated with insomnia was 2.0–5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6–1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7–0.8kg. Thus, vortioxetine (5–20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder. PMID:26864543

  11. Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study

    PubMed Central

    Goemans, Nathalie M.; Tulinius, Már; van den Hauwe, Marleen; Kroksmark, Anna-Karin; Buyse, Gunnar; Wilson, Rosamund J.; van Deutekom, Judith C.; de Kimpe, Sjef J.; Lourbakos, Afrodite; Campion, Giles

    2016-01-01

    Background Drisapersen induces exon 51 skipping during dystrophin pre-mRNA splicing and allows synthesis of partially functional dystrophin in Duchenne muscular dystrophy (DMD) patients with amenable mutations. Methods This 188-week open-label extension of the dose-escalation study assessed the long-term efficacy, safety, and pharmacokinetics of drisapersen (PRO051/GSK2402968), 6 mg/kg subcutaneously, in 12 DMD subjects. Dosing was once weekly for 72 weeks. All subjects had a planned treatment interruption (weeks 73–80), followed by intermittent dosing (weeks 81–188). Results Subjects received a median (range) total dose of 5.93 (5.10 to 6.02) mg/kg drisapersen. After 177 weeks (last efficacy assessment), median (mean [SD]) six-minute walk distance (6MWD) improved by 8 (-24.5 [161]) meters for the 10 subjects able to complete the 6MWD at baseline (mean age [SD]: 9.5 [1.9] years). These statistics include 2 subjects unable to complete the test at later visits and who scored “zero”. When only the 8 ambulant subjects at week 177 were taken into account, a median (mean [SD]) increase of 64 (33 [121]) meters in 6MWD was observed. Of 7 subjects walking ≥330 m at extension baseline, 5 walked farther at week 177. Of 3 subjects walking <330 m, 2 lost ambulation, while 1 declined overall but walked farther at some visits. Over the 188 weeks, the most common adverse events were injection-site reactions, raised urinary α1-microglobulin and proteinuria. Dystrophin expression was detected in all muscle biopsies obtained at week 68 or 72. Conclusion Drisapersen was generally well tolerated over 188 weeks. Possible renal effects, thrombocytopenia and injection-site reactions warrant continued monitoring. Improvements in the 6MWD at 12 weeks were sustained after 3.4 years of dosing for most patients. For a small, uncontrolled study, the outcomes are encouraging, as natural history studies would anticipate a decline of over 100 meters over a 3-year period in a comparable

  12. Efficacy and Safety of Amphotericin B Emulsion versus Liposomal Formulation in Indian Patients with Visceral Leishmaniasis: A Randomized, Open-Label Study

    PubMed Central

    Sundar, Shyam; Pandey, Krishna; Thakur, Chandreshwar Prasad; Jha, Tara Kant; Das, Vidya Nand Ravi; Verma, Neena; Lal, Chandra Shekhar; Verma, Deepak; Alam, Shahnawaz; Das, Pradeep

    2014-01-01

    Background India is home to 60% of the total global visceral leishmaniasis (VL) population. Use of long-term oral (e.g. miltefosine) and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB) lipid emulsion (ABLE) in comparison with that of liposomal formulation (LAmB). Methods In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3∶1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376) or LAmB (N = 124). Initial cure (Day 30/45), clinical improvement (Day 30) and long term definitive cure (Day 180) were assessed. Findings A total of 326 (86.7%) patients in the ABLE group and 122 (98.4%) patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: −0.0663, −0.0150). Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%). Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3%) and chills (18.4% vs. 18.5%) were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3%) compared to LAmB (1.6%). Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group. Conclusions ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability. Trial Registration www.clinicaltrials.gov NCT00876824 PMID:25233346

  13. Efficacy and Safety of Modified Pranlukast (Prakanon®) Compared with Pranlukast (Onon®): A Randomized, Open-Label, Crossover Study

    PubMed Central

    Kim, Seo W.; Kim, Hunam; Ryu, Yon J.; Lee, Jin H.; Shim, Sung S.; Kim, Yoo K.; Chang, Jung H.

    2016-01-01

    Introduction: Pranlukast is a leukotriene receptor antagonist (LTRA) that is used as an additional controller of mild to moderate asthma. This study compared the efficacy and side effects of two bioequivalent preparations of pranlukast: original pranlukast (Onon®; Ono Pharmaceutical, Japan) and a modified formulation of pranlukast (Prakanon®; Yuhan Co, Korea) in patients with mild to moderate asthma. Methods: Of the 34 subjects screened, 30 patients who were using standard medication to control asthma and scored less than 20 points on the Asthma Control Test™ (ACT) were assigned randomly to one of the two groups in a prospective, open label, crossover study: group 1 received Prakanon® (150 mg/day) and group 2 received Onon® (450 mg/day) for 8 weeks each; after a 1-week rest period, the groups were switched to the alternative medication for further 8 weeks and monitored for 2 more weeks without study medication. Evaluation parameters included the ACT, quality of life questionnaire adult Korean asthmatics (QLQAKA), pulmonary function tests, peripheral blood tests, vital signs, and adverse events. Results: Thirty patients were enrolled and 21 completed the trial: 10 in group 1 and 11 in group 2. The baseline data of the two groups did not differ. No statistical significant differences were observed in efficacy and lung function at each time and in changes from baseline value between the two kinds of pranlukast. The final asthma control rate was 81% with Prakanon® and 76% with Onon®. There were no differences in vital signs and laboratory data at each time and in changes from baseline value between the two drugs. There were no differences in adverse events between the two drugs. The most common side effect was abdominal pain. Drug compliance was high, without differences between the two drugs. Conclusion: These findings suggest that Prakanon® which is an improved formulation of pranlukast at a lower dose than the original formulation, Onon®, has a similar

  14. Transcriptomic Profile of Whole Blood Cells from Elderly Subjects Fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG) in a Phase I Open Label Study

    PubMed Central

    Solano-Aguilar, Gloria; Molokin, Aleksey; Botelho, Christine; Fiorino, Anne-Maria; Vinyard, Bryan; Li, Robert; Chen, Celine; Urban, Joseph; Dawson, Harry; Andreyeva, Irina; Haverkamp, Miriam; Hibberd, Patricia L.

    2016-01-01

    We examined gene expression of whole blood cells (WBC) from 11 healthy elderly volunteers participating on a Phase I open label study before and after oral treatment with Lactobacillus rhamnosus GG-ATCC 53103 (LGG)) using RNA-sequencing (RNA-Seq). Elderly patients (65–80 yrs) completed a clinical assessment for health status and had blood drawn for cellular RNA extraction at study admission (Baseline), after 28 days of daily LGG treatment (Day 28) and at the end of the study (Day 56) after LGG treatment had been suspended for 28 days. Treatment compliance was verified by measuring LGG-DNA copy levels detected in host fecal samples. Normalized gene expression levels in WBC RNA were analyzed using a paired design built within three analysis platforms (edgeR, DESeq2 and TSPM) commonly used for gene count data analysis. From the 25,990 transcripts detected, 95 differentially expressed genes (DEGs) were detected in common by all analysis platforms with a nominal significant difference in gene expression at Day 28 following LGG treatment (FDR<0.1; 77 decreased and 18 increased). With a more stringent significance threshold (FDR<0.05), only two genes (FCER2 and LY86), were down-regulated more than 1.5 fold and met the criteria for differential expression across two analysis platforms. The remaining 93 genes were only detected at this threshold level with DESeq2 platform. Data analysis for biological interpretation of DEGs with an absolute fold change of 1.5 revealed down-regulation of overlapping genes involved with Cellular movement, Cell to cell signaling interactions, Immune cell trafficking and Inflammatory response. These data provide evidence for LGG-induced transcriptional modulation in healthy elderly volunteers because pre-treatment transcription levels were restored at 28 days after LGG treatment was stopped. To gain insight into the signaling pathways affected in response to LGG treatment, DEG were mapped using biological pathways and genomic data mining

  15. An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions

    PubMed Central

    Pattee, Gary L.; Wymer, James P.; Lomen-Hoerth, Catherine; Appel, Stanley H.; Formella, Andrea E.; Pope, Laura E.

    2014-01-01

    Abstract Background: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient’s emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. Objective: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Methods: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Clinical trial registration: #NCT00056524. Results: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose

  16. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

    PubMed Central

    Fenaux, Pierre; Mufti, Ghulam J; Hellstrom-Lindberg, Eva; Santini, Valeria; Finelli, Carlo; Giagounidis, Aristoteles; Schoch, Robert; Gattermann, Norbert; Sanz, Guillermo; List, Alan; Gore, Steven D; Seymour, John F; Bennett, John M; Byrd, John; Backstrom, Jay; Zimmerman, Linda; McKenzie, David; Beach, C L; Silverman, Lewis R

    2014-01-01

    Summary Background Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. Methods In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m² per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French–American–British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Findings Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1–26·9), median overall survival was 24·5 months (9·9–not reached) for the azacitidine group versus 15·0 months (5·6–24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43–0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1–58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7–34·3) in the conventional care group (p<0·0001). Peripheral cytopenias were the most

  17. Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren's syndrome: an open-label phase I/II study

    PubMed Central

    Steinfeld, Serge D; Tant, Laure; Burmester, Gerd R; Teoh, Nick KW; Wegener, William A; Goldenberg, David M; Pradier, Olivier

    2006-01-01

    This open-label, phase I/II study investigated the safety and efficacy of epratuzumab, a humanised anti-CD22 monoclonal antibody, in the treatment of patients with active primary Sjögren's syndrome (pSS). Sixteen Caucasian patients (14 females/2 males, 33–72 years) were to receive 4 infusions of 360 mg/m2 epratuzumab once every 2 weeks, with 6 months of follow-up. A composite endpoint involving the Schirmer-I test, unstimulated whole salivary flow, fatigue, erythrocyte sedimentation rate (ESR), and immunoglobulin G (IgG) was devised to provide a clinically meaningful assessment of response, defined as a ≥20% improvement in at least two of the aforementioned parameters, with ≥20% reduction in ESR and/or IgG considered as a single combined criterion. Fourteen patients received all infusions without significant reactions, 1 patient received 3, and another was discontinued due to a mild acute reaction after receiving a partial infusion. Three patients showed moderately elevated levels of Human anti-human (epratuzumab) antibody not associated with clinical manifestations. B-cell levels had mean reductions of 54% and 39% at 6 and 18 weeks, respectively, but T-cell levels, immunoglobulins, and routine safety laboratory tests did not change significantly. Fifty-three percent achieved a clinical response (at ≥20% improvement level) at 6 weeks, with 53%, 47%, and 67% responding at 10, 18, and 32 weeks, respectively. Approximately 40%–50% responded at the ≥30% level, while 10%–45% responded at the ≥50% level for 10–32 weeks. Additionally, statistically significant improvements were observed in fatigue, and patient and physician global assessments. Further, we determined that pSS patients have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy. Thus, epratuzumab appears to be a promising therapy in active pSS, suggesting that further studies be conducted. PMID:16859536

  18. Patient adherence to and tolerability of self-administered interferon β-1a using an electronic autoinjection device: a multicentre, open-label, phase IV study

    PubMed Central

    2012-01-01

    Background Achieving good adherence to self-injected treatments for multiple sclerosis can be difficult. Injection devices may help to overcome some of the injection-related barriers to adherence that can be experienced by patients. We sought to assess short-term adherence to, and tolerability of, interferon (IFN) β-1a administered via electronic autoinjection device in patients with relapsing-remitting multiple sclerosis (RRMS). Methods BRIDGE (RebiSmart to self-inject Rebif serum-free formulation in a multidose cartridge) was a 12-week, multicentre, open-label, single-arm, observational, Phase IV study in which patients self-administered IFN β-1a (titrated to 44 μg), subcutaneously (sc), three times weekly, via electronic autoinjection device. Patients were assessed at baseline and 4-weekly intervals to Week 12 or early termination (ET) for: physical examinations; diary card completion (baseline, Weeks 4, 8 only); neurological examinations (baseline, Week 12/ET only); MS Treatment Concern Questionnaire (MSTCQ; Weeks 4, 8, 12 only); Convenience Questionnaire (Week 12 only); Hospital Anxiety and Depression Scale (HADS); and Paced Auditory Serial Addition Task (PASAT; baseline only). Adherence was defined as administration of ≥ 80% of scheduled injections, recorded by the autoinjection device. Results Overall, 88.2% (105/119; intent-to-treat population) of patients were adherent; 67.2% (80/119) administered all scheduled injections. Medical reasons accounted for 35.6% (31/87) of missed injections, forgetfulness for 20.6% (18/87). Adherence did not correlate with baseline Expanded Disability Status Scale (P = 0.821) or PASAT (P = 0.952) scores, or pre-study therapy (P = 0.303). No significant changes (baseline-Week 12) in mean HADS depression (P = 0.482) or anxiety (P = 0.156) scores were observed. 'Overall convenience' was the most important reported benefit of the autoinjection device. Device features associated with handling and ease of use were highly rated

  19. Comparison of olanzapine long-acting injection and oral olanzapine: a 2-year, randomized, open-label study in outpatients with schizophrenia.

    PubMed

    Detke, Holland C; Weiden, Peter J; Llorca, Pierre-Michel; Choukour, Moutaz; Watson, Susan B; Brunner, Elizabeth; Ascher-Svanum, Haya

    2014-08-01

    We compared long-term treatment effectiveness of monthly olanzapine long-acting injection (LAI) with that of oral olanzapine. Outpatients with 2 or more episodes of psychotic worsening in the past 24 months with Positive and Negative Syndrome Scale total score of lower than 70 were randomized to 405 mg/4 weeks of olanzapine LAI (n = 264) or 10 mg/d of oral olanzapine (n = 260) for 2 years of open-label treatment. Dosing thereafter was flexible (150-405 mg/4 weeks of LAI vs 5-20 mg/d of oral). Primary outcome was time to all-cause discontinuation. At baseline, patients were clinically stable (mean Positive and Negative Syndrome Scale total score of 57). Seventeen percent of patients had been psychiatrically hospitalized in the previous 6 months, and 4.6% were rated nonadherent in the month before study entry. The groups did not differ significantly in median time to all-cause discontinuation (645 days for LAI, 678 days for oral; P = 0.61), discontinuation rate (53.8% for LAI, 51.2% for oral; P = 0.60), or relapse rate (20.1% for LAI, 18.5% for oral; P = 0.66). Postbaseline psychiatric hospitalization rate was low for both groups (7.6% for LAI, 9.2% for oral), but mean hospitalization duration was significantly longer for oral patients (1.80 days [20 for those hospitalized] vs 0.43 days [6 for those hospitalized], P = 0.02). There were no clinically significant group differences in adverse events or safety measures. No post-injection delirium/sedation syndrome events occurred. In conclusion, olanzapine LAI and oral olanzapine were similarly effective and well tolerated for up to 2 years of treatment in patients with schizophrenia. Treatment discontinuation for olanzapine LAI was similar to that of oral olanzapine, despite the 3-hour post-injection observation period and other precautionary procedures related to risk of post-injection delirium/sedation syndrome. PMID:24781441

  20. Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study

    PubMed Central

    Hibi, Toshifumi; Hirohata, Shunsei; Kikuchi, Hirotoshi; Tateishi, Ukihide; Sato, Noriko; Ozaki, Kunihiko; Kondo, Kazuoki; Ishigatsubo, Yoshiaki

    2016-01-01

    Abstract Behçet disease (BD) is a multisystem disease associated with a poor prognosis in cases of gastrointestinal, neurological, or vascular involvement. We conducted a multicenter, prospective, open-label, single-arm phase 3 study to determine the efficacy, safety, and pharmacokinetics of infliximab (IFX) in BD patients with these serious complications who had displayed poor response or intolerance to conventional therapy. IFX at 5 mg/kg was administered to 18 patients (11 intestinal BD, 3 neurological BD [NBD], and 4 vascular BD [VBD]) at weeks 0, 2, and 6 and every 8 weeks thereafter until week 46. In patients who showed inadequate responses to IFX after week 30, the dose was increased to 10 mg/kg. We then calculated the percentage of complete responders according to the predefined criteria depending on the symptoms and results of examinations (ileocolonoscopy, brain magnetic resonance imaging, computed tomography angiography, positron emission tomography, cerebrospinal fluid, or serum inflammatory markers), exploring the percentage of complete responders at week 30 (primary endpoint). The percentage of complete responders was 61% (11/18) at both weeks 14 and 30 and remained the same until week 54. Intestinal BD patients showed improvement in clinical symptoms along with decrease in C-reactive protein (CRP) levels after week 2. Consistently, scarring or healing of the principal ulcers was found in more than 80% of these patients after week 14. NBD patients showed improvement in clinical symptoms, imaging findings, and cerebrospinal fluid examinations. VBD patients showed improvement in clinical symptoms after week 2 with reductions in CRP levels and erythrocyte sedimentation rate. Imaging findings showed reversal of inflammatory changes in 3 of the 4 VBD patients. Irrespective of the type of BD, all patients achieved improvement in quality of life, leading to the dose reduction or withdrawal of steroids. IFX dose was increased to 10 mg/kg in 3

  1. Open-Label Memantine in Fragile X Syndrome

    ERIC Educational Resources Information Center

    Erickson, Craig A.; Mullett, Jennifer E.; McDougle, Christopher J.

    2009-01-01

    Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). The purpose of this pilot study was to examine the effectiveness and tolerability of memantine for a number of target symptoms associated with FXS. Medical records describing open-label treatment with memantine in 6 patients with FXS and a comorbid…

  2. Long-term efficacy and safety of incobotulinumtoxinA and conventional treatment of poststroke arm spasticity: a prospective, non-interventional, open-label, parallel-group study

    PubMed Central

    Dressler, Dirk; Rychlik, Reinhard; Kreimendahl, Fabian; Schnur, Nicole; Lambert-Baumann, Judith

    2015-01-01

    Objective To compare the efficacy and safety of incobotulinumtoxinA with conventional antispastic therapy for poststroke arm spasticity in routine clinical practice over a 1-year period. Design Prospective, non-interventional, open-label, parallel-group study. Setting 47 centres in Germany. Participants Patients with poststroke arm spasticity; 108 receiving incobotulinumtoxinA, 110 conventional therapy. Intervention Conventional antispastic treatment including oral antispastic medications, physiotherapy and occupational therapy or 3-monthly incobotulinumtoxinA injections plus conventional therapy if required. Main outcome measures The main outcome measure was changes in muscle tone (Ashworth Scale) over the 1-year treatment period. Changes in functional disability (Disability Assessment Scale) and quality of life (Short-Form-12 Health Survey) were additionally assessed. Ratings for therapy outcome (Goal Attainment Scale), and efficacy and tolerability of treatment (Global Clinical Impression Scale) were also obtained. Results Muscle tone improved for all spasticity patterns with the Ashworth Scale responder rates between 63% and 86% (incobotulinumtoxinA) and 16–27% (conventional therapy). Median improvement in functional disability was –1.0 (incobotulinumtoxinA) and 0.0 (conventional measures) for all domains. Treatment goals were attained by 93% of incobotulinumtoxinA patients and 30% of patients under conventional therapy. Most physicians (93%) and patients (90%) rated efficacy as good or very good under incobotulinumtoxinA; the proportions were much lower under conventional therapy (36% and 37%). Tolerability under incobotulinumtoxinA was considered good or very good by 99% of physicians and patients (76% and 66%, respectively, under conventional therapy). Quality of life under incobotulinumtoxinA improved by 8.0 (physical score) and 10.8 (mental score) and by 0.8 and 5.7, respectively, under conventional therapy. Conclusions IncobotulinumtoxinA combined

  3. Anti-albuminuric effect of losartan versus amlodipine in hypertensive Japanese patients with type 2 diabetes mellitus: A prospective, open-label, randomized, comparative study

    PubMed Central

    Ohno, Yasuhiro; Nishimura, Akiyoshi; Iwai, Hiroshi; Hirota, Noriyuki; Yamauchi, Takaaki; Fujimoto, Mika; Miyatake, Toshiyuki; Arai, Hiroshi; Aoki, Norihiko

    2007-01-01

    Abstract Background The antiproteinuric effect of the angiotensin II receptor-antagonist losartan has been observed in patients with type 2 diabetes mellitus (T2DM). Proteinuria is considered to be a predictor of the progression of kidney disease. Objective The aims of the present study were to compare and examine the ability of losartan and amlodipine to ameliorate albuminuria in hypertensive Japanese patients (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) with T2DM and whether the change in albuminuria was associated with a change in glomerular filtration rate (GFR). Methods This prospective, open-label, randomized, comparative study was conducted over 3 months at the Kinki University School of Medicine, Osaka-Sayama, Japan. Hypertensive patients with T2DM were enrolled and randomly assigned to 1 of 2 study groups receiving either losartan (25–100 mg/d) or the calcium channel-blocker amlodipine (2.5–5 mg/d). Urinary albumin excretion (UAE), creatinine clearance, and GFR were recorded at study initiation (baseline) and study end (month 3). The GFR was measured from the fractional renal accumulation of 99mTc-diethylenetriaminepentaacetic acid. Adverse events (AEs) were monitored by a clinical research nurse during the examination. Results Fifty patients were asked to enroll and 38 returned the informed written consent. Thirty-five Japanese patients were included in the final study analysis. Seventeen patients were assigned to the losartan group (male sex, 10 [58.8%]; mean [SD] age, 58.1 [8.2] years) and 18 were assigned to the amlodipine group (male sex, 10 [55.6%]; mean [SD] age, 57.4 [8.9] years); no significant between-group difference in demographics was observed. A significant decrease from baseline to month 3 of mean (SD) UAE was observed in the losartan group (352.5 [556.6] mg/d vs 275.7 [466.1] mg/d; P = 0.048). No significant difference in mean (SD) UAE was observed in the amlodipine group for the same time period (298

  4. Single- and multiple-dose pharmacokinetics of genistein capsules in healthy chinese subjects: A phase I, randomized, open-label study

    PubMed Central

    Zeng, Xing; Feng, Yi; Yang, Liu; Huang, Yu; Zhou, Dan; Sun, Jing; Liu, Yiming; Deng, Yuanhui

    2008-01-01

    Background: Genistein capsules are currently being developed to treat osteoporosis in China. Genistein is extracted from the fruit of Sophora japonica Leguminosae. Objective: The objective of this study was to assess the pharmacokinetics of genistein capsules after single and multiple oral doses in healthy Chinese subjects. Methods: This was a Phase I, randomized, open-label, single- and multiple- dose study in healthy Chinese adults (aged 19–40 years). In the single-dose study, subjects were randomly assigned in a 1:1:1 ratio to receive genistein 50, 100, or 300 mg (in 50-mg capsules). To assess the effect of food on the pharmacokinetics, subjects in the 50-mg group were equally randomized again into fasting and postprandial (genistein was administered after a high-fat breakfast) groups according to a 2-way cross-over design. A separate equal-sized group of subjects were administered genistein 50 mg on day 1 (single dose), received no treatment on days 2 and 3, and were administered genistein 50 mg QD for 6 days (days 4–9) to obtain a multiple-dose pharmacokinetic profile. Because genistein is converted so rapidly and completely to glucuronidated genistein after administration, plasma concentrations of glucuronidated genistein were determined using a validated high-performance liquid chromatography/ tandem mass spectrometry method. Drug tolerability was assessed by monitoring adverse events (AEs) and laboratory parameters. Results: The study enrolled 40 healthy subjects (24 men, 16 women; 10 each in the 50-, 100-, and 300-mg single-dose groups and 10 in the multiple-dose group). Three subjects voluntarily withdrew (2 in the 100-mg group and 1 in the 300-mg group) before study drug administration. Thirty-seven subjects (24 men, 13 women) completed the study and were included in the analysis. The mean (SD) values of the single-dose genistein 50-, 100-, and 300-mg groups were as follows: Tmax, 6.0 (2.4), 7.4 (2.4), and 5.6 (1.2) hours, respectively; tl/2, 13.0 (4

  5. Pharmacokinetic properties of lansoprazole (30-mg enteric-coated capsules) and its metabolites: A single-dose, open-label study in healthy Chinese male subjects

    PubMed Central

    Song, Min; Gao, Xuan; Hang, Tai-Jun; Wen, Ai-Dong

    2009-01-01

    Background: Lansoprazole, a benzimidazole derivative, is indicated for the treatment of various peptic diseases. It is metabolized mainly in the liver, and its primary active metabolites present in plasma are 5′-hydroxy lansoprazole and lansoprazole sulfone. Few data are available on the pharmacokinetic properties of lansoprazole, 5′-hydroxy lansoprazole, and lansoprazole sulfone, which can be used to measure cytochrome P450 (CYP) 2C19 activity. Objectives: The aims of this study were to investigate the clinical plasma pharmacokinetic properties of lansoprazole and its metabolites in healthy Chinese male volunteers, and to assess the influences of CYP2C19 on the pharmacokinetics of lansoprazole. Methods: Healthy adult Chinese male volunteers were enrolled in this single-dose, open-label study. All patients received a single oral enteric capsule containing 30 mg of lansoprazole after a 12-hour overnight fast. Serial blood samples were collected immediately before (0 hour) and at 20, 40, 60, 90, 120, and 150 minutes and 3, 4, 6, 8, 10, 12, 15, and 24 hours after study drug administration. The plasma concentrations of lansoprazole, 5′-hydroxy lansoprazole, and lansoprazole sulfone were determined using a validated internal standard high-performance liquid chromatography—tandem mass spectrometry (HPLC-MS/MS) method. Pharmacokinetic properties (including Cmax, Tmax, elimination t½ [t½z], mean residence time [MRT], AUC0–24, AUC0−∞, apparent oral clearance [CLz/F], and apparent volume of distribution [Vz/F]) were determined using the noncompartmental method. Results: Twenty volunteers (mean [SD] age, 34.9 [2.9] years; weight, 64.6 [2.2] kg; height, 171.3 [3.3] cm) were enrolled in and completed the study. The mean (SD) pharmacokinetic properties of lansoprazole were as follows: Cmax, 1047 (344) ng/mL; Tmax, 2.0 (0.7) hours; t½z, 2.24 (1.43) hours; MRT, 3.62 (0.87) hours; AUC0−24, 3388 (1484) ng/mL/h; AUC0-∞, 3496 (1693) ng/mL/h; CLz/F, 9.96 (3.74) L

  6. Pharmacokinetics and Bioequivalence of Two Formulations of Febuxostat 40-Mg and 80-Mg Tablets: A Randomized, Open-Label, 4-Way Crossover Study in Healthy Chinese Male Volunteers

    PubMed Central

    Luo, Zhu; Nan, Feng; Miao, Jia; Chen, Zhihui; Li, Mei; Liang, Maozhi

    2016-01-01

    The present study aimed to investigate the pharmacokinetic properties of febuxostat in healthy Chinese male volunteers and evaluate whether the two formulations of febuxostat 40-mg and 80-mg tablets are bioequivalent. A randomized, open-label, 4-way crossover study was conducted in healthy Chinese male volunteers under fasting conditions. 24 eligible subjects were randomized in a 1:1:1:1 ratio to receive a single dose of test or reference formulation of febuxostat 40-mg or 80-mg tablet. The washout period between each administration was 1 week. Plasma febuxostat was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests. After single-dosing of 1 tablet of 40-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.22±0.87 and 1.85±1.03 h, Cmax 1689.16±461.31 and 1613.80±608.43 ng·mL-1, AUC0-t 5139.87±1349.28 and 5517.91±2024.26 ng·mL-1·h, AUC0−∞ 5263.06±1339.16 and 5640.48±2040.22 ng·mL-1·h, t1/2 4.82±2.61 and 4.85±1.78 h, respectively. After single-dosing of 1 tablet of 80-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.71±1.21 and 2.23±1.55 h, Cmax 2744.47±1157.44 and 2998.17±1200.13 ng·mL-1, AUC0-t 9634.03±2768.25 and 10467.95±3501.65 ng·mL-1·h, AUC0−∞ 9834.32±2730.51 and 10626.63±3504.08 ng·mL-1·h, t1/2 6.25±2.44 and 5.46±1.65 h, respectively. For single-dosing of 1 tablet of 40-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0−∞ and Cmax were 89.79 to 102.55, 90.14 to 102.56 and 93.99 to 129.63, respectively. For single-dosing of 1 tablet of 80-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0−∞ and Cmax were 86.67 to 100.00, 87.50 to 100.51 and 79.48 to 105.99, respectively. This single dose study revealed similar pharmacokinetic properties in

  7. Long-term efficacy and safety of oxycodone–naloxone prolonged release in geriatric patients with moderate-to-severe chronic noncancer pain: a 52-week open-label extension phase study

    PubMed Central

    Guerriero, Fabio; Roberto, Anna; Greco, Maria Teresa; Sgarlata, Carmelo; Rollone, Marco; Corli, Oscar

    2016-01-01

    Background Two-thirds of older people suffer from chronic pain and finding valid treatment options is essential. In this 1-yearlong investigation, we evaluated the efficacy and safety of prolonged-release oxycodone–naloxone (OXN-PR) in patients aged ≥70 (mean 81.7) years. Methods In this open-label prospective study, patients with moderate-to-severe noncancer chronic pain were prescribed OXN-PR for 1 year. The primary endpoint was the proportion of patients who achieved ≥30% reduction in pain intensity after 52 weeks of treatment, without worsening bowel function. The scheduled visits were at baseline (T0), after 4 weeks (T4), and after 52 weeks (T52). Results Fifty patients completed the study. The primary endpoint was achieved in 78% of patients at T4 and 96% at T52 (P<0.0001). Pain intensity, measured on a 0–10 numerical rating scale, decreased from 6.0 at T0 to 2.8 at T4 and to 1.7 at T52 (P<0.0001). Mean daily dose of oxycodone increased from 10 to 14.4 mg (T4) and finally to 17.4 mg (T52). Bowel Function Index from 35.1 to 28.7 at T52. No changes were observed in cognitive functions (Mini-Mental State Examination evaluation), while daily functioning improved (Barthel Index from 53.1 to 61.0, P<0.0001). The Screener and Opioid Assessment for Patients with Pain-Revised score at 52 weeks was 2.6 (standard deviation 1.6), indicating a low risk of aberrant medication-related behavior. In general, OXN-PR was well tolerated. Conclusion This study of the long-term treatment of chronic pain in a geriatric population with OXN-PR shows satisfying analgesic effects achieved with a stable low daily dose, coupled with a good safety profile and, in particular, with a reduction of constipation, often present during opioid therapy. Our findings support the indications of the American Geriatrics Society, suggesting the use of opioids to treat pain in older people not responsive to acetaminophen or nonsteroidal anti-inflammatory drugs. PMID:27143857

  8. A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg

    PubMed Central

    Festin, Mario P.R.; Bahamondes, Luis; Nguyen, Thi My Huong; Habib, Ndema; Thamkhantho, Manopchai; Singh, Kuldip; Gosavi, Arundhati; Bartfai, Gyorgy; Bito, Tamas; Bahamondes, M. Valeria; Kapp, Nathalie

    2016-01-01

    STUDY QUESTION Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method? SUMMARY ANSWER Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population. WHAT IS KNOWN ALREADY LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception. STUDY DESIGN, SIZE, DURATION This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 330 healthy fertile women aged 18–45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability

  9. A multi-center, prospective, open-label, 8-week study of certoparin for anticoagulation during maintenance hemodialysis – the membrane study

    PubMed Central

    2012-01-01

    Background Adequate anticoagulation is prerequisite for effective hemodialysis to prevent clotting in the extracorporeal circuit. We aimed providing first data on the efficacy and safety of the low-molecular-weight heparin certoparin in this setting. Methods Multicenter, open-label, 8-week trial. Patients received a single dose of 3,000 IU certoparin i.v. with additional titration steps of 600 IU and/or continuous infusion if necessary. Results 120 patients were screened, 109 enrolled (median age 71; range 26–90 years) and 106 available for efficacy analyses. The percentage of unsatisfactory dialysis results at 8 weeks due to clotting or bleeding, was 1.9% (n = 2/106; 95% confidence interval [CI] 0.23–6.65%); no major bleeding. 1.9% had moderate/severe clotting in the lines/bubble catcher and 2.8% in the dialyser at week 8. 15.7 ± 14.3% of the dialysis filters’ visual surface area was showing redness. In subgroups of patients receiving median doses of 3000 ± 0, 3000 (2400–6000) and 4200 (3000–6600) IU, plasma aXa levels at baseline, 4 and 8 weeks were 0.24 [95%CI 0.21–0.27], 0.33 [0.27–0.40] and 0.38 [0.33–0.45] aXa IU/ml at 2 h. C48h was 0.01 [0.01–0.02] aXa IU at all visits. At baseline and 4 weeks AUC0-48h was 2.66 [2.19–3.24] and 3.66 [3.00–4.45] aXa IU*h/ml. In 3.0% of dialyses (n = 83/2724) prolonged fistula compression times were documented. Eight patients (7.34%) had at least one episode of minor bleeding. 4) 85.3% of patients had any adverse event, 9.2% were serious without suspected drug relation; and in 32 patients a drug-relation was suspected. Conclusions Certoparin appears effective and safe for anticoagulation in patients undergoing maintenance hemodialysis. PMID:22742742

  10. Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and curcumin: a randomized, double-blind placebo-controlled cross-over 4g study and an open-label 8g extension study.

    PubMed

    Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev

    2012-05-01

    Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) represent useful models for studying multiple myeloma precursor disease, and for developing early intervention strategies. Administering a 4g dose of curcumin, we performed a randomised, double-blind placebo-controlled cross-over study, followed by an open-label extension study using an 8g dose to assess the effect of curcumin on FLC response and bone turnover in patients with MGUS and SMM. 36 patients (19 MGUS and 17 SMM) were randomised into two groups: one received 4g curcumin and the other 4g placebo, crossing over at 3 months. At completion of the 4g arm, all patients were given the option of entering an open-label, 8g dose extension study. Blood and urine samples were collected at specified intervals for specific marker analyses. Group values are expressed as mean ± 1 SD. Data from different time intervals within groups were compared using Student's paired t-test. 25 patients completed the 4g cross-over study and 18 the 8g extension study. Curcumin therapy decreased the free light-chain ratio (rFLC), reduced the difference between clonal and nonclonal light-chain (dFLC) and involved free light-chain (iFLC). uDPYD, a marker of bone resorption, decreased in the curcumin arm and increased on the placebo arm. Serum creatinine levels tended to diminish on curcumin therapy. These findings suggest that curcumin might have the potential to slow the disease process in patients with MGUS and SMM. PMID:22473809

  11. Improvement of executive functions in boys with attention deficit hyperactivity disorder: an open-label follow-up study with once-daily atomoxetine.

    PubMed

    Gau, Susan Shur-Fen; Shang, Chi-Yung

    2010-03-01

    Atomoxetine is efficacious in reducing symptoms of attention deficit hyperactivity disorder (ADHD) but its effect on executive functions needs more investigation. We examined the effect of atomoxetine on a wide range of non-verbal executive functions among 30 drug-naive male patients with DSM-IV ADHD, aged 8-16 yr, in an open-label 12-wk atomoxetine treatment trial. Before administration of atomoxetine, the participants were assessed by psychiatric interviews, the WISC-III, and the tasks involving executive functions of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-dimensional/Extra-dimensional Shifts (IED), Rapid Visual Information Processing (RVIP), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC); and reassessed at weeks 4 and 12. All the raw scores of the CANTAB were transformed to z scores based on a normative sample of 180 children aged 8-16 yr. Results showed significant improvement in executive functions after treatment with atomoxetine for 4 wk or 12 wk including improved shifting and flexibility of attention in the IED; improved spatial short-term memory in the SSP; improved sustained attention and increased response inhibition in the RVIP; improved spatial working memory in the SWM; and improved spatial planning and problem solving in the SOC. Our findings suggested that atomoxetine was associated with significant improvement in various non-verbal executive functions among boys with ADHD, in addition to its well-known efficacy in ADHD-related symptom reductions. However, owing to lack of a placebo-controlled trial design, the findings should be interpreted with caution that changes in performance may be due to practice effects.

  12. A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain.

    PubMed

    Hoggart, B; Ratcliffe, S; Ehler, E; Simpson, K H; Hovorka, J; Lejčko, J; Taylor, L; Lauder, H; Serpell, M

    2015-01-01

    Peripheral neuropathic pain (PNP) poses a significant clinical challenge. The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated in this 38-week open-label extension study. In total, 380 patients with PNP associated with diabetes or allodynia entered this study from two parent randomised, controlled trials. Patients received THC/CBD spray for a further 38 weeks in addition to their current analgesic therapy. Neuropathic pain severity was the primary efficacy measure using a pain 0-10 numerical rating scale (NRS). Additional efficacy, safety and tolerability outcomes were also investigated. In total, 234 patients completed the study (62 %). The pain NRS showed a decrease in score over time in patients from a mean of 6.9 points (baseline in the parent studies) to a mean of 4.2 points (end of open-label follow-up). The proportion of patients who reported at least a clinically relevant 30 % improvement in pain continued to increase with time (up to 9 months); at least half of all patients reported a 30 % improvement at all time points. Improvements were observed for all secondary efficacy outcomes, including sleep quality 0-10 NRS scores, neuropathic pain scale scores, subject global impression of change and EQ-5D questionnaire scores. THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use. In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia.

  13. A phase 2, multicenter, open-label study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma

    PubMed Central

    Kudchadkar, Ragini; Ernst, Scott; Chmielowski, Bartosz; Redman, Bruce G; Steinberg, Joyce; Keating, Anne; Jie, Fei; Chen, Caroline; Gonzalez, Rene; Weber, Jeffrey

    2015-01-01

    Survivin is a microtubule-associated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a first-in-class survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6-month progression-free survival (PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel. The study had two parts: Part 1 established the dose of docetaxel that was tolerable in combination with YM155, and Part 2 evaluated the tolerable docetaxel dose (75 mg/m2) in combination with YM155 (5 mg/m2 per day continuous infusion over 168 h every 3 weeks). The primary endpoint was 6-month PFS rate. Secondary endpoints were objective response rate (ORR), 1-year overall survival (OS) rate, time from first response to progression, clinical benefit rate (CBR), and safety. Sixty-four patients with metastatic melanoma were treated with docetaxel and YM155. Eight patients received an initial docetaxel dose of 100 mg/m2 and 56 patients received 75 mg/m2 of docetaxel. Six-month PFS rate per Independent Review Committee (IRC) was 34.8% (n = 64; 95% CI, 21.3–48.6%), and per Investigator was 31.3% (n = 64; 95% CI, 19.5–43.9%). The best ORR (complete response [CR] + partial response [PR]) per IRC was 12.5% (8/64). The stable disease (SD) rate was 51.6% (33/64), leading to a CBR (CR + PR + SD) of 64.1% (41/64). Estimated probability of 1-year survival was 56.3%. YM155 is a novel agent showing modest activity when combined with docetaxel for treating patients with melanoma. YM155 was generally well tolerated, but the predetermined primary efficacy endpoint (i.e., 6-month PFS rate ≥20%) was not achieved. PMID:25533314

  14. Open-Label Study of the Influence of Food Containing the Royal Sun Mushroom, Agaricus brasiliensis KA21 (Higher Basidiomycetes), on the Quality of Life of Healthy Human Volunteers.

    PubMed

    Motoi, Masuro; Motoi, Akitomo; Yamanaka, Daisuke; Ohno, Naohito

    2015-01-01

    We conducted an open-label study in which food containing Agaricus brasiliensis KA21 was consumed continuously for 12 weeks. A questionnaire for subjective evaluation of the efficacy of this food (hereafter, subjective evaluation questionnaire) revealed significant improvements compared with before its intake; there were improvements in the scores of the amounts of hair loss and gray hair, fatigue and general malaise, eye strain, shoulder stiffness, coldness of extremities, difficulty staying awake during the day, and ease of getting out of bed. These findings suggest that intake of food containing A. brasiliensis KA21 results in the above-mentioned subjectively evaluated improvements, and the possibility that A. brasiliensis KA21 improves the body's immunity. Moreover, no issues regarding the safety of the test food were found.

  15. A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia

    PubMed Central

    2013-01-01

    Background We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). Methods Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). Results There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was

  16. Clinical safety of insulin detemir in patients with Type 2 diabetes in the Gulf countries: The multicenter, noninterventional, open-label LevSafe study

    PubMed Central

    El Shiekh, Abdel Rahman; Farrag, Hesham A.; Ashour, Tarek; Alshali, Khalid Zaki; AbdelFattah, Waleed

    2016-01-01

    Aim: To evaluate the safety profile of insulin detemir (IDet) in people with Type 2 diabetes mellitus (T2DM) in the Gulf countries in the 32-week, noninterventional LevSafe study. Methods: People with T2DM whose physicians had opted to start IDet therapy were included in the study. Safety parameters, including serious adverse drug reactions (SADRs) and hypoglycemia, and changes in body weight and glycemic control were evaluated at baseline, week 16 and week 32. Results: A total of 686 patients were exposed to IDet therapy with a mean (±standard deviation) age, body mass index, and diabetes duration of 51.3 ± 11.0 years, 31.3 ± 5.5 kg/m2, and 10.2 ± 6.1 years, respectively. The mean total daily dose of IDet was 32.0 ± 32.8 U at baseline and 44.7 ± 60.7 U at week 32. No SADRs were reported during the study. Total hypoglycemia decreased from 435 events at baseline to 204 events at week 32 (mean change analyzed by Wilcoxon signed rank test: −0.34; P = 0.0115), and no major hypoglycemia was reported at week 32. Over the 32-week treatment period, the mean body weight decreased from 85.7 ± 15.2 kg to 85.4 ± 14.5 kg (P = 0.0203), glycated hemoglobin A1c from 9.9 ± 1.67% to 7.7 ± 1.36% (P < 0.0001), and fasting plasma glucose from 11.9 ± 3.27 mmol/L to 7.4 ± 1.85 mmol/L (P < 0.0001). Conclusion: IDet therapy was well-tolerated and was associated with a decreased number of hypoglycemic events and improved glycemic control after 32 weeks in patients with T2DM in the Gulf countries. PMID:27366709

  17. PROJECT TALENT, 1-YEAR FOLLOW-UP STUDIES.

    ERIC Educational Resources Information Center

    COOLEY, WILLIAM W.; FLANAGAN, JOHN C.

    THE "PROJECT TALENT" FOLLOWUP STUDIES WERE CONCERNED WITH VARIOUS ASPECTS OF CAREER DEVELOPMENT OF AMERICAN YOUTH, CONSISTING PRIMARILY OF THE EDUCATIONAL AND VOCATIONAL PLANS AND DECISIONS WHICH ONE MAKES DURING HIGH SCHOOL AND IMMEDIATELY FOLLOWING HIGH SCHOOL. RELATIONSHIPS WERE SOUGHT BETWEEN TRAITS EXHIBITED BY STUDENTS IN HIGH SCHOOL AND…

  18. Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study.

    PubMed

    Taher, Ali T; Cappellini, M Domenica; Aydinok, Yesim; Porter, John B; Karakas, Zeynep; Viprakasit, Vip; Siritanaratkul, Noppadol; Kattamis, Antonis; Wang, Candace; Zhu, Zewen; Joaquin, Victor; Uwamahoro, Marie José; Lai, Yong-Rong

    2016-03-01

    Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10mg/kg/day. Mean actual dose±SD over 1year was 14.70±5.48mg/kg/day. At week 52, mean LIC±SD decreased significantly from 15.13±10.72mg Fe/g dw at baseline to 8.46±6.25mg Fe/g dw (absolute change from baseline, -6.68±7.02mg Fe/g dw [95% CI: -7.91, -5.45]; P<0.0001). Most common drug-related adverse events were gastrointestinal: abdominal discomfort, diarrhoea and nausea (n=6 each). There was one death (pneumonia, not considered drug related). With significant and clinically relevant reductions in iron burden alongside a safety profile similar to that in THALASSA, these data support earlier escalation with higher deferasirox doses in iron-overloaded non-transfusion-dependent anaemia patients.

  19. Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study.

    PubMed

    Taher, Ali T; Cappellini, M Domenica; Aydinok, Yesim; Porter, John B; Karakas, Zeynep; Viprakasit, Vip; Siritanaratkul, Noppadol; Kattamis, Antonis; Wang, Candace; Zhu, Zewen; Joaquin, Victor; Uwamahoro, Marie José; Lai, Yong-Rong

    2016-03-01

    Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10mg/kg/day. Mean actual dose±SD over 1year was 14.70±5.48mg/kg/day. At week 52, mean LIC±SD decreased significantly from 15.13±10.72mg Fe/g dw at baseline to 8.46±6.25mg Fe/g dw (absolute change from baseline, -6.68±7.02mg Fe/g dw [95% CI: -7.91, -5.45]; P<0.0001). Most common drug-related adverse events were gastrointestinal: abdominal discomfort, diarrhoea and nausea (n=6 each). There was one death (pneumonia, not considered drug related). With significant and clinically relevant reductions in iron burden alongside a safety profile similar to that in THALASSA, these data support earlier escalation with higher deferasirox doses in iron-overloaded non-transfusion-dependent anaemia patients. PMID:26852651

  20. A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study)

    PubMed Central

    Mcgowan, Ian; Cranston, Ross D.; Duffill, Kathryn; Siegel, Aaron; Engstrom, Jarret C.; Nikiforov, Alexyi; Jacobson, Cindy; Rehman, Khaja K.; Elliott, Julie; Khanukhova, Elena; Abebe, Kaleab; Mauck, Christine; Spiegel, Hans M. L.; Dezzutti, Charlene S.; Rohan, Lisa C.; Marzinke, Mark A.; Hiruy, Hiwot; Hendrix, Craig W.; Richardson-Harman, Nicola; Anton, Peter A.

    2015-01-01

    Objectives The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK), and pharmacodynamics (PD) of three tenofovir (TFV) gels for rectal application. The vaginal formulation (VF) gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF) gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF) gel was also evaluated in the CHARM-01 study. Methods Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial. Results All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC) TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively). Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection. Conclusions All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection. Trial Registration ClinicalTrials.gov NCT01575405 PMID:25942472

  1. An open-label cohort study of the improvement of quality of life and pain in de novo cervical dystonia patients after injections with 500 U botulinum toxin A (Dysport)

    PubMed Central

    Hefter, H; Benecke, R; Erbguth, F; Jost, W; Reichel, G; Wissel, J

    2013-01-01

    Objectives It remains to be determined whether the benefits of botulinum toxin type A (BoNT-A) on cervical dystonia (CD) motor symptoms extend to improvements in patient's quality of life (QoL). This analysis of a large, multicentre study was conducted with the aim of investigating changes in QoL and functioning among de novo patients receiving 500 U BoNT-A (abobotulinumtoxinA; Dysport) for the treatment of the two most frequent forms of CD, predominantly torticollis and laterocollis. Design A prospective, open-label study of Dysport (500 U; Ipsen Biopharm Ltd) administered according to a defined intramuscular injection algorithm. Setting German and Austrian outpatient clinics. Participants 516 male and female patients (aged ≥18 years) with de novo CD. The majority of patients had torticollis (78.1%). 35 patients had concomitant depression (MedDRA-defined). Main outcome measures Change from baseline to weeks 4 and 12 in Craniocervical Dystonia Questionnaire (CDQ-24) total and subscale scores, patient diary items (‘day-to-day capacities and activities’, ‘pain’ and ‘duration of pain’) and global assessment of pain. Results Significant improvements were observed in CDQ-24 total and subscale scores at week 4 and were sustained up to week 12 (p<0.001). Changes in CDQ-24 scores did not significantly differ between the torticollis and laterocollis groups or between patients with or without depression. There were also significant reductions in patient diary item scores for activities of daily living, pain and pain duration at weeks 4 and 12 (p<0.001). Pain relief (less or no pain) was reported by 66% and 74.1% of patients at weeks 4 and 12, respectively. Changes in pain parameters demonstrated a positive relationship with change in Tsui score. Conclusions After standardised open-label treatment with Dysport 500 U, improvements in QoL and pain intensity up to 12 weeks in patients with CD were observed. PMID:23604344

  2. The mixed amphetamine salt extended release (Adderall XR, Max-XR) as an adjunctive to SSRIS or SNRIS in the treatment of adult ADHD patients with comorbid partially responsive generalized anxiety: an open-label study.

    PubMed

    Gabriel, Adel

    2010-06-01

    To examine the changes in partially responsive anxiety symptoms utilizing adjunctive treatment with the mixed amphetamine salt extended release (Adderall XR, MAX-XR) in the treatment of adult ADHD patients, with comorbid refractory anxiety. Consenting adult patients (n = 32) with confirmed diagnosis of generalized anxiety (GA) and comorbid (ADHD) participated in this open-label study. All patients had significant comorbid anxiety symptoms (HAM-A > 7) and failed to respond to 8-week trials of Serotonin Reuptake Inhibitors (SSRIs) or Norepinephrine Reuptake inhibitors (SNRIs). All patients were treated with the "Mixed Amphetamine salts Extended Release Adderall XR, (MAS-XR), as adjunctive to SSRIs or to SNRIs and were followed for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression severity subscale (CGI-S). Other scales included the Hamilton Anxiety Scale (HAM-A), the adult ADHD Self-Report Scale (ASRS-v1.1) symptom checklist, and Sheehan's disability scale. Baseline measures prior to the treatment with MAS-XR were compared to those at 4, 8, and at 12 weeks of treatment. Monitoring for pulse, blood pressure, and weight changes was carried out at baseline and at end point. All patients completed this open-label trial. There was significant and robust resolution of symptoms of all effectiveness measures, including the symptoms of anxiety, as shown by changes from baseline in HAM-A, ASRS-v1.1, and CGI at 8 weeks. Also there was significant reduction in the disability score at 12 weeks. Patients tolerated the treatment, and there were no significant cardiovascular changes at 12 weeks. There was decrease in mean weight at 12 weeks by 2.2 kg (P < .001). Mixed amphetamine salts MAS-XR can be used in adult patients with ADHD and comorbid anxiety symptoms. Larger controlled studies are needed to support the effectiveness of mixed amphetamine salts in patients with comorbid anxiety symptoms. Treatments need to include the targeting of the

  3. Duloxetine in OsteoArthritis (DOA) study: study protocol of a pragmatic open-label randomised controlled trial assessing the effect of preoperative pain treatment on postoperative outcome after total hip or knee arthroplasty

    PubMed Central

    Blikman, T; Rienstra, W; van Raaij, T M; ten Hagen, A J; Dijkstra, B; Zijlstra, W P; Bulstra, S K; van den Akker-Scheek, I; Stevens, M

    2016-01-01

    Introduction Residual pain is a major factor in patient dissatisfaction following total hip arthroplasty or total knee arthroplasty (THA/TKA). The proportion of patients with unfavourable long-term residual pain is high, ranging from 7% to 34%. There are studies indicating that a preoperative degree of central sensitisation (CS) is associated with poorer postoperative outcomes and residual pain. It is thus hypothesised that preoperative treatment of CS could enhance postoperative outcomes. Duloxetine has been shown to be effective for several chronic pain syndromes, including knee osteoarthritis (OA), in which CS is most likely one of the underlying pain mechanisms. This study aims to evaluate the postoperative effects of preoperative screening and targeted duloxetine treatment of CS on residual pain compared with care-as-usual. Methods and analysis This multicentre, pragmatic, prospective, open-label, randomised controlled trial includes patients with idiopathic hip/knee OA who are on a waiting list for primary THA/TKA. Patients at risk for CS will be randomly allocated to the preoperative duloxetine treatment programme group or the care-as-usual control group. The primary end point is the degree of postoperative pain 6 months after THA/TKA. Secondary end points at multiple time points up to 12 months postoperatively are: pain, neuropathic pain-like symptoms, (pain) sensitisation, pain catastrophising, joint-associated problems, physical activity, health-related quality of life, depressive and anxiety symptoms, and perceived improvement. Data will be analysed on an intention-to-treat basis. Ethics and dissemination The study is approved by the local Medical Ethics Committee (METc 2014/087) and will be conducted according to the principles of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard (GCP), and in compliance with the Medical Research Involving Human Subjects Act (WMO). Trial registration number 2013-004313-41; Pre

  4. A Prospective, Open-label Study to Compare the Efficacy and the Safety of Topical Loteprednol Etabonate and Topical Flurbiprofen Sodium in Patients with Post-Operative Inflammation after Cataract Extraction

    PubMed Central

    Bannale, Sheshidhar G.; Pundarikaksha, H.P.; Sowbhagya, H.N.

    2012-01-01

    Purpose To study the effect of the topical Non-Steroidal Anti Inflammatory Drug (NSAID), Flurbiprofen 0.03%, as an alternative to the topical steroids for the postoperative control of inflammation in cataract surgeries. Methods The effect of the topical NSAID, flurbiprofen sodium 0.03%, was studied and compared with that of the topical steroid – Loteprednol etabonate 0.5% suspension (as eye drops) in a prospective, open labelled study. Both the groups (20 patients each) were similar in the baseline parameters. The postoperative inflammatory response following the standard, small incision, extra capsular cataract extraction was assessed in both the groups for 28 post-operative days. The parameters which were considered for the study were conjunctival hyperaemia, ciliary congestion, corneal oedema, cells in the anterior chamber, aqueous flare and ocular pain. The severity of the postoperative inflammatory responses for both the drugs was graded on the post-operative days 1, 7, 14, 21 and 28 and it was statistically analyzed. Results The 2 groups did not differ statistically in the effect of the treatment for any of the variables, which included aqueous cells, flare, ciliary congestion and conjunctival congestion (p< 0.001). Both the drugs were well tolerated and no severe adverse Drug Reactions (ADRs) were caused by the topical NSAID and the topical steroid. Conclusion The topical NSAID, Flurbiprofen, is as effective as the topical corticosteroid, Loteprednol and it can be used as an alternative in the routine postoperative treatment following uncomplicated cataract surgeries. PMID:23285440

  5. A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia.

    PubMed

    Awan, Farrukh T; Hillmen, Peter; Hellmann, Andrzej; Robak, Tadeusz; Hughes, Steven G; Trone, Denise; Shannon, Megan; Flinn, Ian W; Byrd, John C

    2014-11-01

    Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.

  6. Efficacy, adherence and tolerability of once daily tenofovir DF-containing antiretroviral therapy in former injecting drug users with HIV-1 receiving opiate treatment: results of a 48-week open-label study

    PubMed Central

    2011-01-01

    Objective To assess efficacy, adherence and tolerability of once daily antiretroviral therapy containing tenofovir disoproxil fumarate (DF) 300 mg in HIV-1-infected former injecting drug users receiving opiate treatment (IVDU). Methods European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-naïve, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment. Results Sixty-seven patients were enrolled in the study and 41 patients completed treatment. In the primary analysis (intent-to-treat missing = failure) at week 48, 34% of patients (23/67; 95% CI: 23%-47%) had plasma HIV-1 RNA < 50 copies/mL. Using an intent-totreat missing = excluded approach, the week 48 proportion of patients with plasma HIV-1 RNA < 50 copies/mL increased to 56% (23/41; 95% CI: 40%-72%). Mean (standard deviation) increase from baseline in CD4+ cell count at week 48 was 176 (242) cells/mm3. Although self-reported adherence appeared high, there were high levels of missing data and adherence results should be treated with caution. No new safety issues were identified. Conclusions Levels of missing data were high in this difficult-to-treat population, but potent antiretroviral suppression was achieved in a substantial proportion of HIV-infected IVDU-patients. PMID:22024421

  7. Pharmacokinetic profile of rizatriptan 10-mg tablet and 10-mg orally disintegrating tablet administered with or without water in healthy subjects: an open-label, randomized, single-dose, 3-period crossover study.

    PubMed

    Swan, Suzanne K; Alcorn, Harry; Rodgers, Anthony; Hustad, Carolyn M; Ramsey, Karen E; Woll, Susan; Skobieranda, Franck

    2006-02-01

    This open-label, 3-period crossover study compared the plasma concentration profiles of rizatriptan tablet, orally disintegrating tablet with water (ODTc), and ODT without water (ODTs) in 24 healthy volunteers aged 18 to 45 years. At each period, subjects received a single dose of either 10-mg rizatriptan tablet, 10-mg rizatriptan ODTs, or 10-mg rizatriptan ODTc. The authors hypothesized that ODTc has a greater geometric mean AUC(0-2h) than ODTs and that ODTc has a greater geometric mean AUC(0-1h) than tablet. A secondary end point was to compare the time of occurrence of the maximum rizatriptan plasma concentration (t(max)) of each dosing method. ODTc had a statistically significantly greater geometric mean AUC(0-2h) compared with ODTs (33.84 h x ng/mL vs 18.83 h x ng/mL; P < .001). ODTc had a slightly, but not statistically significantly, greater geometric mean AUC(0-1h) compared with rizatriptan tablet (17.07 h x ng/mL vs 13.32 h x ng/mL). The median t(max) was 0.67 hours for ODTc and tablet and 1.33 hours for ODTs. ODTc showed a slightly, but not significantly, faster rate of absorption compared with tablet. ODTs with water had a faster rate of absorption than ODTc. Future studies are needed to determine whether this pharmacokinetic difference produces differential efficacy in a clinical setting. PMID:16432269

  8. Effects of an ethyl lactate shampoo in conjunction with a systemic antibiotic in the treatment of canine superficial bacterial pyoderma in an open-label, nonplacebo-controlled study.

    PubMed

    de Jaham, Caroline

    2003-01-01

    An open-label, nonplacebo-controlled study was designed to compare systemic cephalexin therapy versus systemic cephalexin and ethyl lactate shampoo therapy in the treatment of canine superficial bacterial pyoderma. Twenty client-owned dogs diagnosed with generalized superficial bacterial pyoderma (SP) were alternately assigned to oral treatment with cephalexin (25 to 30 mg/kg every 12 hours) or treatment with cephalexin (as for Group 1) and twice-weekly shampooing with a 10% ethyl lactate shampoo, which was left in contact with the dog's skin for 10 minutes. On Days 14 and 28, skin lesion severity scores, assessed by the investigators, were significantly (P <.01) lower for the group treated with cephalexin and shampoo than for the group treated with cephalexin only. On Day 14, dog owners gave better scores to dogs treated with cephalexin and shampoo for haircoat appearance and body odor than for dogs treated only with cephalexin. Clinical and cytologic resolution of SP occurred significantly (P <.02) sooner in the cephalexin/shampoo group (29.4 days) than in the cephalexin only group (37.8 days).

  9. Vagus nerve stimulation therapy: 2-year prospective open-label study of 40 subjects with refractory epilepsy and low IQ who are living in long-term care facilities.

    PubMed

    Huf, Roger L; Mamelak, Adam; Kneedy-Cayem, Kara

    2005-05-01

    Treating seizures among patients with mental retardation/developmental disabilities (MR/DD) is difficult owing in large part to the presence of additional comorbidities and the resulting need for polytherapy. Therefore, a nonpharmacological treatment option is needed for this population. This prospective, open-label study documented the long-term outcome of 40 low-IQ (<70) patients living in long-term care facilities who received vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. Subjects were seen every 1 to 3 months by their neurologist (R.H.). Seizure frequency, antiepileptic medication, and quality-of-life information were documented preimplantation and quarterly thereafter through 2 years. The surgery and therapy were well tolerated. Seizures were reduced by at least 50% for 11 subjects. Antiepileptic medications were reduced from 3.3 per subject at baseline to an average of 2.3 per subject after 2 years. According to caregiver reports, overall quality of life improved for the majority of subjects; also, using the Client Development Evaluation Report (CDER), statistically significant improvements were reported at both 1 and 2 years in attention span, word usage, clarity of speech, standing balance, washing dishes, and household chores. VNS is a viable treatment option for low-IQ patients with pharmacoresistant epilepsy who are living in long-term care facilities. PMID:15820352

  10. An Open-Label Study of Risperidone in the Improvement of Quality of Life and Treatment of Symptoms of Violent and Self-Injurious Behaviour in Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Read, Stephen G.; Rendall, Maureen

    2007-01-01

    Background: We examined the benefits of risperidone, including quality of life (QoL), in the treatment of violent and self-injurious behaviour in adults with moderate, severe or profound intellectual disability. Methods: Twenty-four participants received open-label, oral, flexible-dose risperidone of 0.5-6 mg/day for 12 weeks. Efficacy was…

  11. An Open-Label, Noncomparative, Multicenter Study to Evaluate Efficacy and Safety of NASHA/Dx Gel as a Bulking Agent for the Treatment of Fecal Incontinence

    PubMed Central

    Dodi, Giuseppe; Jongen, Johannes; de la Portilla, Fernando; Raval, Manoj; Altomare, Donato F.; Lehur, Paul-Antoine

    2010-01-01

    Fecal incontinence (FI) is the involuntary loss of rectal contents through the anal canal. Reports of its prevalence vary from 1–21%. Studies, have demonstrated a positive effect on FI symptoms with injectable bulking agents. This study evaluated the safety and efficacy of NASHA/Dx gel in the treatment of FI. One hundred fifteen eligible patients suffering from FI received 4 injections of 1 mL NASHA/Dx gel. Primary efficacy was based on data from 86 patients that completed the study. This study demonstrated a ≥50% reduction from baseline in the number of FI episodes in 57.1% of patients at 6 months, and 64.0% at 12 months. Significant improvements (P < .001) were also noted in total number of both solid and loose FI episodes, FI free days, CCFIS, and FIQL scores in all 4 domains. The majority of the treatment related AEs (94.9%) were mild or moderate intensity, and (98.7%) of AEs resolved spontaneously, or following treatment, without sequelae. Results of this study indicate NASHA/Dx gel was efficacious in the treatment of FI. Treatment effect was significant both in reduction of number of FI episodes and disease specific quality of life at 6 months and lasted up to 12 months after treatment. PMID:21234379

  12. A multicentric, open label, randomised, postmarketing efficacy study comparing multidose of lincomycin hydrochloride capsule 500 mg with multidose cefpodoxime proxetil tablet 200 mg in patients with tonsillitis, sinusitis.

    PubMed

    Kothadiya, Ajay

    2012-08-01

    Tonsillitis causes considerable short and medium term morbidity, and can be recurrent. Sinusitis can be acute (less than 4 weeks), subacute (4-8 weeks) or chronic (8 weeks or more). To study the comparative efficacy and safety of multidose treatments of lincomycin hydrochloride 500 mg capsules against cefpodoxime proxetil 200 mg tablets on its outcome in the Indian scenario are the aims and objective of the study. A total of 41 tonsillitis, sinusitis cases of either gender aged above 18 years were enrolled in the study. The diagnosis of sonsillitis, sinusitis was made based on examination of symptoms and throat swab. A randomised treatment of either lincomycin hydrochloride 500 mg capsules or cefpodoxime proxetil 200 mg tablets twice daily for five days alongwith other concomitant medications depending on related symptoms was given to 40 patients. At the end of study, all patients were re-evaluated and the response rate was assessed. The most common clinical symptoms were body temperature, headache, throat pain, postnasal discharge, mucopus, odynophagia, sinus tenderness, nasal congestion, pharyngeal congestion and tonsillar congestion. The overall response rate of lincomycin hydrochloride in all the symptoms except headache was more effective than cefpodoxime proxetil. Out of 100% (n = 20) patients in each group, 67.89% in lincomycin and 52.27% in cefpodoxime patients achieved complete relief, in all the clinical symptoms. The study suggests that lincomycin hydrochloride capsules, a conventional antibiotic indicates effective treatment for relief from tonsillitis and sinusitis, as compared to new third generation antibiotic.

  13. An open-label pilot study to evaluate the efficacy and tolerability of a silicone gel in the treatment of hypertrophic scars using clinical and ultrasound assessments.

    PubMed

    Lacarrubba, Francesco; Patania, Lara; Perrotta, Rosario; Stracuzzi, Giorgio; Nasca, Maria Rita; Micali, Giuseppe

    2008-01-01

    Silicone gel sheets and intralesional corticosteroids are effective treatments for hypertrophic scars according to evidence studies. The aim of this study was to evaluate, both clinically and by ultrasound, the efficacy and tolerability of a topical self-drying silicone gel containing polysiloxane and silicone dioxide applied twice daily in eight hypertrophic scars. After 6 months all lesions showed evident clinical and/or ultrasound improvement, with a mean scar thickness reduction of 37% (range 20-54%). Although controlled trials in larger series of patients are necessary, our results suggest that the self-drying silicone gel may represent a safe and effective treatment for hypertrophic scars.

  14. A prospective randomised open label study to evaluate the potential of a new silver alginate/carboxymethylcellulose antimicrobial wound dressing to promote wound healing.

    PubMed

    Beele, Hilde; Meuleneire, Frans; Nahuys, Marc; Percival, Steven L

    2010-08-01

    The aim of this study was to observe both the clinical signs and symptoms of wounds at risk of infection, that is critically colonised (biofilm infected) and antimicrobial-performance of an ionic silver alginate/carboxymethylcellulose (SACMC) dressing, in comparison with a non silver calcium alginate fibre (AF) dressing, on chronic venous leg and pressure ulcers. Thirty-six patients with venous or pressure ulcers, considered clinically to be critically colonised (biofilm infected), were randomly chosen to receive either an SACMC dressing or a non silver calcium AF dressing. The efficacy of each wound dressing was evaluated over a 4-week period. The primary study endpoints were prevention of infection and progression to wound healing. The SACMC group showed a statistically significant (P = 0.017) improvement to healing as indicated by a reduction in the surface area of the wound, over the 4-week study period, compared with AF controls. In conclusion, the SACMC dressing showed a greater ability to prevent wounds progressing to infection when compared with the AF control dressing. In addition, the results of this study also showed an improvement in wound healing for SACMC when compared with a non silver dressing.

  15. Reduced Silent Occlusions with a Novel Catheter Infusion Set (BD FlowSmart): Results from Two Open-Label Comparative Studies

    PubMed Central

    Gibney, Michael; Xue, Zhenyi; Swinney, Monica; Bialonczyk, Damian

    2016-01-01

    Abstract Background: Insulin pump users experience periods of unexplained hyperglycemia. In some cases these may be due to insulin flow interruptions termed “silent occlusions,” which occur without activating the pump alarm and may require set replacement. Materials and Methods: In-line pressure profiles of a novel infusion set with a 6-mm, 28-gauge polymer, dual-ported catheter (BD FlowSmart™; Becton Dickinson and Co., Franklin Lakes, NJ) were compared with those of an existing infusion set (Quick-set®; Medtronic MiniMed, Northridge, CA) in two separate studies involving insulin diluent infusions over 2.5–4.5-h periods in healthy adults without diabetes. Study 1, a pilot study (n = 25), compared the occurrence of flow interruption events (silent occlusions and/or occlusion alarms) between the two infusion sets and between manual or device-assisted insertion methods. Study 2 (n = 60) was designed to show ≥50% reduction in flow interruption events with the BD set after manual insertions. (Silent occlusions were defined by a continuous pressure rise for ≥30 min.) Results: In Study 1, significantly fewer silent occlusions were seen with BD FlowSmart versus Quick-set infusion sets for both manual (three of 22 [13.6%] vs. 12 of 24 [50%]; P = 0.012) and mechanical (two of 24 [8.3%] vs. nine of 25 [36%]; P = 0.037) insertions, yielding risk reductions of 73% (95% confidence interval [CI], 25–91%) and 77% (95% CI, 17–94%), respectively. In Study 2, flow interruption events occurred in three of 117 (2.6%) and 12 of 118 (10.2%) BD FlowSmart and Quick-set infusion sets, respectively, yielding a 75% risk reduction (95% CI, 20–92%; P = 0.030). Percentage of time with flow interruption was significantly lower with BD sets in both studies (P < 0.02). Leakage (>0.5 IU or 5 μL) occurred infrequently and did not differ between sets. Conclusions: A novel side-ported insulin infusion set demonstrated significant reductions in flow

  16. Efficacy and Safety of a Hyaluronic Acid Filler to Correct Aesthetically Detracting or Deficient Features of the Asian Nose: A Prospective, Open-Label, Long-Term Study

    PubMed Central

    Liew, Steven; Scamp, Terrence; de Maio, Mauricio; Halstead, Michael; Johnston, Nicole; Silberberg, Michael; Rogers, John D.

    2016-01-01

    Background There is increasing interest among patients and plastic surgeons for alternatives to rhinoplasty, a common surgical procedure performed in Asia. Objectives To evaluate the safety, efficacy, and longevity of a hyaluronic acid filler in the correction of aesthetically detracting or deficient features of the Asian nose. Methods Twenty-nine carefully screened Asian patients had their noses corrected with the study filler (Juvéderm VOLUMA [Allergan plc, Dublin, Ireland] with lidocaine injectable gel), reflecting individualized treatment goals and utilizing a standardized injection procedure, and were followed for over 12 months. Results A clinically meaningful correction (≥1 grade improvement on the Assessment of Aesthetic Improvement Scale) was achieved in 27 (93.1%) patients at the first follow-up visit. This was maintained in 28 (96.6%) patients at the final visit, based on the independent assessments of a central non-injecting physician and the patients. At this final visit, 23 (79.3%) patients were satisfied or very satisfied with the study filler and 25 (86.2%) would recommend it to others. In this small series of patients, there were no serious adverse events (AEs), with all treatment-related AEs being mild to moderate, transient injection site reactions, unrelated to the study filler. Conclusions Using specific eligibility criteria, individualized treatment goals, and a standardized injection procedure, the study filler corrected aesthetically detracting or deficient features of the Asian nose, with the therapeutic effects lasting for over 12 months, consistent with a high degree of patient satisfaction. This study supports the safety and efficacy of this HA filler for specific nose augmentation procedures in selected Asian patients. Level of Evidence: 3 Therapeutic PMID:27301371

  17. Multicentre, prospective, randomised, open-label, blinded end point trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study

    PubMed Central

    Ford, Ian; Walker, Andrew; Hawkey, Chris; Begg, Alan; Avery, Anthony; Taggar, Jaspal; Wei, Li; Struthers, Allan D; MacDonald, Thomas M

    2016-01-01

    Introduction Ischaemic heart disease (IHD) is one of the most common causes of death in the UK and treatment of patients with IHD costs the National Health System (NHS) billions of pounds each year. Allopurinol is a xanthine oxidase inhibitor used to prevent gout that also has several positive effects on the cardiovascular system. The ALL-HEART study aims to determine whether allopurinol improves cardiovascular outcomes in patients with IHD. Methods and analysis The ALL-HEART study is a multicentre, controlled, prospective, randomised, open-label blinded end point (PROBE) trial of allopurinol (up to 600 mg daily) versus no treatment in a 1:1 ratio, added to usual care, in 5215 patients aged 60 years and over with IHD. Patients are followed up by electronic record linkage and annual questionnaires for an average of 4 years. The primary outcome is the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes include all-cause mortality, quality of life and cost-effectiveness of allopurinol. The study will end when 631 adjudicated primary outcomes have occurred. The study is powered at 80% to detect a 20% reduction in the primary end point for the intervention. Patient recruitment to the ALL-HEART study started in February 2014. Ethics and dissemination The study received ethical approval from the East of Scotland Research Ethics Service (EoSRES) REC 2 (13/ES/0104). The study is event-driven and results are expected after 2019. Results will be reported in peer-reviewed journals and at scientific meetings. Results will also be disseminated to guideline committees, NHS organisations and patient groups. Trial registration number 32017426, pre-results. PMID:27609859

  18. Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol

    PubMed Central

    Dickstein, Yaakov; Leibovici, Leonard; Yahav, Dafna; Eliakim-Raz, Noa; Daikos, George L; Skiada, Anna; Antoniadou, Anastasia; Carmeli, Yehuda; Nutman, Amir; Levi, Inbar; Adler, Amos; Durante-Mangoni, Emanuele; Andini, Roberto; Cavezza, Giusi; Mouton, Johan W; Wijma, Rixt A; Theuretzbacher, Ursula; Friberg, Lena E; Kristoffersson, Anders N; Zusman, Oren; Koppel, Fidi; Dishon Benattar, Yael; Altunin, Sergey; Paul, Mical

    2016-01-01

    Introduction The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification. Methods and analysis This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin–meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings. Ethics and dissemination The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The

  19. Rationale and study design of the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose finding trial

    PubMed Central

    Waldron-Lynch, Frank; Kareclas, Paula; Irons, Kathryn; Walker, Neil M; Mander, Adrian; Wicker, Linda S; Todd, John A; Bond, Simon

    2014-01-01

    Introduction CD4 T regulatory cells (Tregs) are crucial for the maintenance of self-tolerance and are deficient in many common autoimmune diseases such as type 1 diabetes (T1D). Interleukin 2 (IL-2) plays a major role in the activation and function of Tregs and treatment with ultra-low dose (ULD) IL-2 could increase Treg function to potentially halt disease progression in T1D. However, prior to embarking on large phase II/III clinical trials it is critical to develop new strategies for determining the mechanism of action of ULD IL-2 in participants with T1D. In this mechanistic study we will combine a novel trial design with a clinical grade Treg assay to identify the best doses of ULD IL-2 to induce targeted increases in Tregs. Method and analysis Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D) is a single centre non-randomised, single dose, open label, adaptive dose-finding trial. The primary objective of DILT1D is to identify the best doses of IL-2 to achieve a minimal or maximal Treg increase in participants with T1D (N=40). The design has an initial learning phase where pairs of participants are assigned to five preassigned doses followed by an interim analysis to determine the two Treg targets for the reminder of the trial. This will then be followed by an adaptive phase which is fully sequential with an interim analysis after each participant is observed to determine the choice of dose based on the optimality criterion to minimise the determinant of covariance of the estimated target doses. A dose determining committee will review all data available at the interim(s) and then provide decisions regarding the choice of dose to administer to subsequent participants. Ethics and dissemination Ethical approval for the study was granted on 18 February 2013. Results The results of this study will be reported through peer-reviewed journals, conference presentations and an internal organisational report. Trial registration numbers NCT

  20. Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study

    PubMed Central

    Truman, Lucy A; Pekalski, Marcin L; Kareclas, Paula; Evangelou, Marina; Walker, Neil M; Howlett, James; Mander, Adrian P; Kennet, Jane; Wicker, Linda S; Bond, Simon; Todd, John A; Waldron-Lynch, Frank

    2015-01-01

    Introduction Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing β cells in the pancreatic islets, leading to insulinopenia and hyperglycaemia. Genetic analyses indicate that alterations of the interleukin-2 (IL-2) pathway mediating immune activation and tolerance predispose to T1D, specifically the polymorphic expression of the IL-2 receptor-α chain (CD25) on T lymphocytes. Replacement of physiological doses of IL-2 could restore self-tolerance and prevent further autoimmunity by enhancing the function of CD4+ T regulatory cells (Tregs) to limit the activation of auto reactive T effector cells (Teffs). In this experimental medicine study, we use an adaptive trial design to determine the optimal dosing regimen for IL-2 to improve Treg function while limiting activation of Teffs in participants with T1D. Methods and analysis The Adaptive study of IL-2 dose frequency on Tregs in type 1 diabetes(DILfrequency) is a mechanistic, non-randomised, repeat dose open-label, response-adaptive study of 36 participants with T1D. The objective is to establish the optimal dose and frequency of ultra-low dose IL-2: to increase Treg frequency within the physiological range, to increase CD25 expression on Tregs, without increasing CD4+ Teffs. DILfrequency has an initial learning phase where 12 participants are allocated to six different doses and frequencies followed by an interim statistical analysis. After analysis of the learning phase, the Dose and Frequency Committee will select the optimal targets for Treg frequency, Treg CD25 expression and Teff frequency. Three groups of eight participants will be treated consecutively in the confirming phase. Each dose and frequency selected will be based on statistical analysis of all data collected from the previous groups. Ethics Ethical approval for DILfrequency was granted on 12 August 2014. Results The results of this study will be reported, through peer-reviewed journals, conference presentations and

  1. An open-label study on the effect of flax seed powder (Linum usitatissimum) supplementation in the management of diabetes mellitus.

    PubMed

    Mani, Uliyar Vitaldas; Mani, Indirani; Biswas, Mamta; Kumar, Smriti Nanda

    2011-09-01

    Diabetes mellitus is characterized by hyperglycemia and associated with aberrations in the metabolism of carbohydrate, protein, and lipid that result in development of secondary complications. Extensive studies have indicated that nutritional therapy plays a pivotal role in the controlling or postponing of development of these secondary complications. Several functional foods have been shown to possess hypoglycemic and hypolipidemic properties. Flax seed (FS) is a functional food that is rich in omega 3 fatty acids and antioxidants and is low in carbohydrates. In exploratory studies, FS was incorporated in recipes, which resulted in a reduction in the glycemic index of the food items. These observations prompted us to investigate the efficacy of FS supplementation in type 2 diabetics (n = 29). Subjects were assigned to the experimental (n = 18) or the control group (n = 11) on the basis of their desire to participate in the study. The experimental group's diet was supplemented daily with 10 g of FS powder for a period of 1 month. The control group received no supplementation or placebo. During the study, diet and drug intake of the subjects remained unaltered. The efficacy of supplementation with FS was evaluated through a battery of clinico-biochemical parameters. Supplementation with FS reduced fasting blood glucose by 19.7% and glycated hemoglobin by 15.6%. A favorable reduction in total cholesterol (14.3%), triglycerides (17.5%), low-density lipoprotein cholesterol (21.8%), and apolipoprotein B and an increase in high-density lipoprotein cholesterol (11.9%) were also noticed. These observations suggest the therapeutic potential of FS in the management of diabetes mellitus.

  2. An open-label study on the effect of flax seed powder (Linum usitatissimum) supplementation in the management of diabetes mellitus.

    PubMed

    Mani, Uliyar Vitaldas; Mani, Indirani; Biswas, Mamta; Kumar, Smriti Nanda

    2011-09-01

    Diabetes mellitus is characterized by hyperglycemia and associated with aberrations in the metabolism of carbohydrate, protein, and lipid that result in development of secondary complications. Extensive studies have indicated that nutritional therapy plays a pivotal role in the controlling or postponing of development of these secondary complications. Several functional foods have been shown to possess hypoglycemic and hypolipidemic properties. Flax seed (FS) is a functional food that is rich in omega 3 fatty acids and antioxidants and is low in carbohydrates. In exploratory studies, FS was incorporated in recipes, which resulted in a reduction in the glycemic index of the food items. These observations prompted us to investigate the efficacy of FS supplementation in type 2 diabetics (n = 29). Subjects were assigned to the experimental (n = 18) or the control group (n = 11) on the basis of their desire to participate in the study. The experimental group's diet was supplemented daily with 10 g of FS powder for a period of 1 month. The control group received no supplementation or placebo. During the study, diet and drug intake of the subjects remained unaltered. The efficacy of supplementation with FS was evaluated through a battery of clinico-biochemical parameters. Supplementation with FS reduced fasting blood glucose by 19.7% and glycated hemoglobin by 15.6%. A favorable reduction in total cholesterol (14.3%), triglycerides (17.5%), low-density lipoprotein cholesterol (21.8%), and apolipoprotein B and an increase in high-density lipoprotein cholesterol (11.9%) were also noticed. These observations suggest the therapeutic potential of FS in the management of diabetes mellitus. PMID:22432725

  3. A Medical Food Formulation of Griffonia simplicifolia/Magnesium for Childhood Periodic Syndrome Therapy: An Open-Label Study on Motion Sickness.

    PubMed

    Esposito, Maria; Precenzano, Francesco; Sorrentino, Michele; Avolio, Deborah; Carotenuto, Marco

    2015-08-01

    Motion sickness (MS) is a disabling condition dominated by disagreement between visually perceived movement and the vestibular system's sense of movement, with symptoms like dizziness, fatigue, and nausea, and other autonomic disabling symptoms. Preparations of Griffonia simplicifolia, containing high concentrations of 5-HTP, might be effective for serotonin-related disorders, including MS. Therefore, the aim of the present study is to assess the efficacy and safety of the G. simplicifolia/magnesium complex in a pediatric population with MS. The Griffonia/magnesium complex (50 and 200 mg, respectively) was orally administered as a prophylactic therapy for MS twice a day for 3 months to group A, and no therapy for MS was administered to group B. The MS clinical signs were recorded by parents or, where possible, directly from children by a specific module, which included validated questions for the diagnoses that were administered to all subjects and parents of both groups. Two study groups were matched for age (P=.224), sex (P=.801), and z-score body-mass index (P=.173). At T0, all recruited subjects in both groups complained about MS. After 3 months (T1), group A showed an MS prevalence of 36%, significantly lower than MS prevalence in group B (73%) (P<.001). The findings of the present study suggest the role of the Griffonia/magnesium complex as a potential treatment with middle-term efficacy even for MS. PMID:25590358

  4. Usability of a novel disposable autoinjector device for ixekizumab: results from a qualitative study and an open-label clinical trial, including patient-reported experience

    PubMed Central

    Callis Duffin, Kristina; Bukhalo, Michael; Bobonich, Margaret A; Shrom, David; Zhao, Fangyi; Kershner, James R; Gill, Anne; Pangallo, Beth; Shuler, Catherine L; Bagel, Jerry

    2016-01-01

    Background Most biologic therapies for psoriasis are delivered via subcutaneous injection. Ixekizumab, an anti-interleukin 17A monoclonal antibody approved for patients with moderate-to-severe plaque psoriasis, is delivered subcutaneously via prefilled syringe or autoinjector. Here we report the results of an ixekizumab autoinjector usability study as well as the patient-reported experience with the autoinjector in a clinical trial. Methods The usability study enrolled 49 subjects (patients with a range of autoimmune conditions or their caregivers). Subjects were randomized to a trained or untrained group and were evaluated for their ability to perform an injection successfully when provided the device and the instructions for use. In the clinical trial, 102 subjects (patients with psoriasis or their caregivers) used the autoinjector to deliver injections of ixekizumab (80 mg every 2 weeks after a starting dose of 160 mg). At weeks 0, 4, and 8, subjects completed the subcutaneous administration assessment questionnaire, which assesses the ease of use and confidence with using an injection device. Results In the usability study, all subjects in the untrained arm performed successful injections, while two subjects in the trained arm had an injection failure. These incidences were not consistent with any pattern of issues with the device or the instructions for use. In the clinical trial, there were two injection failures of 674 total self-injections performed over 12 weeks. At the first use of the device, 95% of subjects either agreed or strongly agreed that the device was “overall easy to use”, and they felt “confident the dose was complete” according to the subcutaneous administration assessment questionnaire. Conclusion The ixekizumab autoinjector was used successfully by patients and caregivers with or without training. Subjects using the autoinjector in a clinical trial felt it was easy to use and felt confident while using it. PMID:27785115

  5. Comparative clinical profile of mirtazapine and duloxetine in practical clinical settings in Japan: a 4-week open-label, parallel-group study of major depressive disorder

    PubMed Central

    Nagao, Kei; Kishi, Taro; Moriwaki, Masatsugu; Fujita, Kiyoshi; Hirano, Shigeki; Yamanouchi, Yoshio; Funahashi, Toshihiko; Iwata, Nakao

    2013-01-01

    No studies have compared mirtazapine with duloxetine in patients with major depressive disorder (MDD). Fifty-six patients were nonrandomly assigned to a 4-week treatment with either 15 to 45 mg/day of mirtazapine (n = 22) or 20 to 60 mg/day of duloxetine (n = 34). The primary efficacy measurements were the Hamilton Rating Scale for Depression (HRSD) and the Montgomery–Åsberg Depression 6-point Rating Scale (MADRS) scores. The second efficacy measurements were the response and remission rates of treatment. Tolerability assessments were also performed. Fifty-six patients (43 male; age, 43.6 years) were recruited. There was no significant difference in the discontinuation rate between the mirtazapine and duloxetine treatment groups (P = 0.867). Both mirtazapine and duloxetine significantly improved the HRSD and MADRS scores from baseline (P < 0.0001–0.0004). While mirtazapine was superior to duloxetine in the reduction of HRSD scores (P = 0.0421), there was no significant change in MADRS scores in terms of between-group differences (P = 0.171). While more somnolence was observed with mirtazapine (P = 0.0399), more nausea was associated with duloxetine (P = 0.0089). No serious adverse events were observed for either antidepressant. Mirtazapine and duloxetine were safe and well-tolerated treatments for Japanese patients with MDD. Double-blind controlled studies are needed to further explore the efficacy and safety of mirtazapine and duloxetine in Japanese patients with MDD. PMID:23766648

  6. Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects.

    PubMed

    Qayyum, Aisha; Najmi, Muzammil Hasan; Abbas, Mateen

    2013-11-01

    Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen (100mg) either generic or branded product according to randomization scheme on each of 2 periods. Blood samples were collected and plasma flurbiprofen concentration was determined by a validated HPLC method. Pharmacokinetic parameters like AUC(0-t), AUC(0-oo), Cmax, Tmax, t½, Vd and clearance were determined. The 90% CI for the ratio of geometric means of test to reference product's pharmacokinetic variables was calculated. Pharmacokinetic parameters for two formulations were comparable. Ratio of means of AUC(0-24), AUC(0-oo) and Cmax for test to reference products and 90% CI for these ratios were within the acceptable range. The p-values calculated by TOST were much less than the specified value (p-0.05). ANOVA gave p-values which were more than the specified value (p-0.05) for sequence, subject, period and formulation. Test formulation of flurbiprofen (tablet Flurso) was found to meet the criteria for bioequivalence to branded product (tablet Ansaid) based on pharmacokinetic parameters.

  7. Reboxetine for ADHD in children non-responders or with poor tolerance to methylphenidate: a prospective long-term open-label study.

    PubMed

    Quintero, Javier; López-Muñoz, Francisco; Alamo, Cecilio; Loro, Mercedes; García-Campos, Natalia

    2010-11-01

    Up to 30% of patients with attention-deficit hyperactivity disorder (ADHD) treated with psychostimulants discontinue the treatment because of intolerance or lack of therapeutic response. Therapeutic alternatives are needed for such patients. In the present case series, we study the effectiveness of reboxetine over a period of 6 months in a sample of 14 children diagnosed with ADHD according to DSM-IV-TR criteria, who had responded only partially or had presented poor tolerance to conventional treatment with methylphenidate. Clinical efficacy was evaluated through the application of the 18-item Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). Percentages of responders (ADHD-RS ≥ 25%) and improvers (CGI-I absolute value < 4) were 90.9 and 72.7%, respectively. No serious side-effects were observed during treatment, the most frequent effects being headaches and insomnia. The initial findings of our study show that reboxetine may constitute an effective tool for long-term treatment of children with ADHD who present poor response or poor tolerance to initial treatment with methylphenidate.

  8. An open label study of the use of EEG biofeedback using beta training to reduce anxiety for patients with cardiac events

    PubMed Central

    Michael, Anne John; Krishnaswamy, Saroja; Mohamed, Jamaludin

    2005-01-01

    Objective To establish the effectiveness of EEG biofeedback using beta training as a relaxation technique and ultimately reducing anxiety levels of patients with confirmed unstable angina or myocardial infarction. Methodology Patients with confirmed unstable angina or myocardial infarction referred by cardiologists were recruited 2–3 days after their cardiac event from the cardiology wards. Their initial anxiety scores were determined using the Hospital Anxiety and Depression Scale. Those that returned for therapy underwent instrument feedback training using EEG every two weeks for a total of five sessions. EEG frequencies were measured for all sessions. Dropouts who did not participate in the program agreed to return 3 months later for the second psychological assessment. The study design was uncontrolled. Results Subjects had significantly lower anxiety scores at the second screening (p < 0.001), while the dropouts had significantly higher scores (p < 0.001). Beta training was effective in increasing sensory motor rhythm (SMR) waves but no significant effect was present for the alpha waves. Conclusions The uncontrolled nature of the study limits firm conclusions. However, the significantly lowered anxiety scores for subjects and enhancing of SMR waves indicate the effectiveness of beta training as a promising approach to EEG biofeedback for anxiety reduction. PMID:18568116

  9. A phase 1, open-label, dose-escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma.

    PubMed

    Dunn, Tamara J; Dinner, Shira; Price, Elizabeth; Coutré, Steven E; Gotlib, Jason; Hao, Ying; Berube, Caroline; Medeiros, Bruno C; Liedtke, Michaela

    2016-04-01

    Pralatrexate inhibits folic acid metabolism, and preclinical studies have shown that it is cytotoxic to multiple myeloma cells. This phase 1 study investigated the safety and efficacy of pralatrexate in combination with bortezomib in adults with relapsed or refractory multiple myeloma. A standard 3 + 3 design was used. Patients received intravenous pralatrexate at doses ranging from 10 to 30 mg/m(2) and intravenous bortezomib at a dose of 1·3 mg/m(2) on days 1, 8 and 15 of each 4-week cycle. Eleven patients were enrolled and completed a median of two cycles. The maximum tolerated dose was 20 mg/m(2) . Two patients experienced dose-limiting toxicity of mucositis. The most frequent non-haematological toxicities were fatigue (55%) and mucositis (45%). There were three serious adverse events in three patients: rash, sepsis and hypotension. One patient (9%) had a very good partial response, 1 (9%) had a partial response, 1 (9%) had minimal response and two (18%) had progressive disease. The median duration of response was 4 months, the median time to next treatment was 3·4 months and the median time to progression was 4 months. Pralatrexate, in combination with bortezomib, was generally safe and demonstrated modest activity in relapsed or refractory multiple myeloma. Clinicaltrials.gov identifier: NCT01114282.

  10. Efficacy of a classical antiobesity Unani pharmacopial formulation (Safoof-e-Muhazzil) in systolic and diastolic blood pressure: A randomized, open-labeled, controlled clinical study

    PubMed Central

    Khan, Asim Ali; Jahangir, Umar; Jalees, Farhan; Kapoor, Prem; Urooj, Shaista

    2013-01-01

    The aim of this study is to evaluate the efficacy of a Unani formulation in hypertension. A total of 90 patients with total cholesterol level of more than 220 mg/dl with associated conditions were included in this study. A total of 30 patients having a mean systolic blood pressure (BP) of 133.86 mmHg comprising Group A received Unani formulation Safoof-e-Muhazzil (SM) in its classical powder form in the dose of 5 g twice a day orally. Group B comprising of 30 patients with a mean systolic BP of 133.13 mmHg received same drug, but in compressed tablet form in the same dosage, whereas, 30 patients comprising Group C with a mean systolic BP of 129.45 mmHg, received Atorvastatin 10 mg as a standard control. Patients were evaluated on each follow-up at 2nd, 4th and 6th week. The mean systolic BP in Group A and B before treatment was 133.86 ± 3.028 mmHg and 133.13 ± 2.852 mmHg, which significantly decreased to 119.33 ± 1.922 mmHg (P < 0.001) and 119 ± 1.760 mmHg (P < 0.001) respectively. In the control Group C before treatment BP was 129.45 ± 2.499 mmHg and after treatment it significantly decreased to 124.34 ± 1.794 mmHg (P < 0.01). The percentage change after treatment was 10.85%, 10.61% and 3.94% respectively in each group. Mean diastolic BP in Group A and B before treatment was 85.06 ± 2.11 mmHg and 84.56 ± 1.5 mmHg, which significantly decreased to 79.06 ± 1.56 mmHg (P < 0.001) and 79.96 ± 1.15 mmHg (P < 0.001) respectively, BP before treatment in Group C was 83.23 ± 1.588 mmHg, which was decreased to 124.34 ± 1.794 mmHg (P < 0.01). The study results indicate that the test drug was quite effective in reducing both systolic as well as diastolic BP. PMID:24350049

  11. An open-label pilot study of the use of rivastigmine to promote functional recovery in patients with unilateral spatial neglect due to first ischemic stroke.

    PubMed

    Paolucci, Stefano; Bureca, Ivana; Multari, Mirella; Nocentini, Ugo; Matano, Alessandro

    2010-01-01

    The aim of this study was to evaluate the efficacy and safety of rivastigmine as add-on treatment to specific cognitive rehabilitation for unilateral spatial neglect (USN). Twenty patients were randomly assigned either to rehabilitation treatment only (No-RIV) or to rivastigmine (3 mg twice a day, for 8 weeks) add-on treatment (RIV+,). USN and functional status were evaluated by means of specific and validated instruments at baseline, at discharge and at one-month follow up. Compared with the untreated patients, the RIV+ subjects, at discharge, recorded significantly better discharge scores and higher effectiveness on two of the scales. However, subsequent further improvement of the No-RIV patients meant that at follow up there was no significant difference between the two groups. No other statistically significant difference was found. Rivastigmine as add-on treatment to specific cognitive training for USN may improve and accelerate recovery on some specific impairment tests as compared with cognitive training alone.

  12. Fecal Microbiota Transplant for Relapsing Clostridium difficile Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized, Open-Label, Controlled Pilot Study

    PubMed Central

    Youngster, Ilan; Sauk, Jenny; Pindar, Christina; Wilson, Robin G.; Kaplan, Jess L.; Smith, Mark B.; Alm, Eric J.; Gevers, Dirk; Russell, George H.; Hohmann, Elizabeth L.

    2014-01-01

    Background. Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration. Methods. Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires. Results. A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2–16) relapses prior to study enrollment, with 5 (range, 3–15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5–10) the day prior to FMT to 2 (IQR, 1–2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2–6) before transplant to 8 (IQR, 5–9) after transplant. No serious or unexpected adverse events occurred. Conclusions. In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration. Clinical Trials Registration. NCT01704937. PMID:24762631

  13. Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate.

    PubMed

    Ford, C; Goodman, A D; Johnson, K; Kachuck, N; Lindsey, J W; Lisak, R; Luzzio, C; Myers, L; Panitch, H; Preiningerova, J; Pruitt, A; Rose, J; Rus, H; Wolinsky, J

    2010-03-01

    The ongoing US Glatiramer Acetate (GA) Trial is the longest evaluation of continuous immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to evaluate up to 15 years of GA as a sole disease-modifying therapy. Two hundred and thirty-two patients received at least one GA dose since study initiation in 1991 (mITT cohort), and 100 (43%, Ongoing cohort) continued as of February 2008. Patients were evaluated every 6 months using the Expanded Disability Status Scale (EDSS). Mean GA exposures were 8.6 +/- 5.2, 4.81 +/- 3.69, and 13.6 +/- 1.3 years and mean disease durations were 17, 13, and 22 years for mITT, Withdrawn and Ongoing cohorts, respectively. For Ongoing patients, annual relapse rates (ARRs) maintained a decline from 1.12 +/- 0.82 at baseline to 0.25 +/- 0.34 per year; 57% had stable/improved EDSS scores (change < or = 0.5 points); 65% had not transitioned to secondary progressive multiple sclerosis (SPMS); 38%, 18%, and 3% reached EDSS 4, 6, and 8. For all patients on GA therapy (the mITT cohort), ARRs declined from 1.18 +/- 0.82 to 0.43 +/- 0.58 per year; 54% had stable/improved EDSS scores; 75% had not transitioned to SPMS; 39%, 23%, and 5% reached EDSS 4, 6, and 8. In conclusion, multiple sclerosis patients with mean disease duration of 22 years administering GA for up to 15 years had reduced relapse rates, and decreased disability progression and transition to SPMS. There were no long-term safety issues.

  14. The effects of the multispecies probiotic mixture Ecologic®Barrier on migraine: results of an open-label pilot study.

    PubMed

    de Roos, N M; Giezenaar, C G T; Rovers, J M P; Witteman, B J M; Smits, M G; van Hemert, S

    2015-01-01

    Migraine prevalence is associated with gastrointestinal disorders. Possible underlying mechanisms could be increased gut permeability and inflammation. Probiotics may decrease intestinal permeability as well as inflammation, and therefore may reduce the frequency and/or intensity of migraine attacks. Therefore we assessed feasibility, possible clinical efficacy, and adverse reactions of probiotic treatment in migraine patients. 29 migraine patients took 2 g/d of a probiotic food supplement (Ecologic(®)Barrier, 2.5×10(9) cfu/g) during 12 weeks. Participants recorded frequency and intensity of migraine in a headache diary and completed the Migraine Disability Assessment Scale (MIDAS) and Henry Ford Hospital Headache Disability Inventory (HDI) at baseline and after 12 weeks of treatment. Compliance was measured every 4 weeks by counting the remaining sachets with probiotics. The study was completed by 27/29 (93%) patients who took 95% of the supplements. Obstipation was reported by 4 patients during the first 2 weeks of treatment only. The mean±standard deviation (SD) number of migraine days/month decreased significantly from 6.7±2.4 at baseline to 5.1±2.2 (P=0.008) in week 5-8 and 5.2±2.4 in week 9-12 (P=0.001). The mean±SD intensity of migraine decreased significantly from 6.3±1.5 at baseline to 5.5±1.9 after treatment (P=0.005). The MIDAS score improved from 24.8±25.5 to 16.6±13.5 (P=0.031). However, the mean HDI did not change significantly. In conclusion, probiotics may decrease migraine supporting a possible role for the intestine in migraine management. Feasibility and lack of adverse reactions justify further placebo-controlled studies.

  15. Randomized Open-Label Pilot Study of the Influence of Probiotics and the Gut Microbiome on Toxic Metal Levels in Tanzanian Pregnant Women and School Children

    PubMed Central

    Bisanz, Jordan E.; Enos, Megan K.; Mwanga, Joseph R.; Changalucha, John; Burton, Jeremy P.; Gloor, Gregory B.

    2014-01-01

    ABSTRACT Exposure to environmental toxins is a 21st century global health problem that is often the result of dietary intake. Although efforts are made to reduce dietary toxin levels, they are often unsuccessful, warranting research into novel methods to reduce host exposure. Food-grade microbes that can be delivered to the gastrointestinal tract and that are capable of sequestering toxins present a safe and cost-effective intervention. We sought to investigate the potential for probiotic-supplemented yogurt to lower heavy metal levels in at-risk populations of pregnant women and in children in Mwanza, Tanzania, and to examine the microbiome in relation to toxin levels. Two populations suspected to have high toxic metal exposures were studied. A group of 44 school-aged children was followed over 25 days, and 60 pregnant women were followed over their last two trimesters until birth. A yogurt containing 1010 CFU Lactobacillus rhamnosus GR-1 per 250 g was administered, while control groups received either whole milk or no intervention. Changes in blood metal levels were assessed, and the gut microbiomes of the children were profiled by analyzing 16S rRNA sequencing via the Ion Torrent platform. The children and pregnant women in the study were found to have elevated blood levels of lead and mercury compared to age- and sex-matched Canadians. Consumption of probiotic yogurt had a protective effect against further increases in mercury (3.2 nmol/liter; P = 0.035) and arsenic (2.3 nmol/liter; P = 0.011) blood levels in the pregnant women, but this trend was not statistically significant in the children. Elevated blood lead was associated with increases in Succinivibrionaceae and Gammaproteobacteria relative abundance levels in stool. PMID:25293764

  16. Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study

    PubMed Central

    Hafner, Patricia; Bonati, Ulrike; Erne, Beat; Schmid, Maurice; Rubino, Daniela; Pohlman, Urs; Peters, Thomas; Rutz, Erich; Frank, Stephan; Neuhaus, Cornelia; Deuster, Stefanie; Gloor, Monika; Bieri, Oliver; Fischmann, Arne; Sinnreich, Michael; Gueven, Nuri; Fischer, Dirk

    2016-01-01

    Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients. Trial Registration ClinicalTrials.gov NCT02516085 PMID:26799743

  17. A 2013/2014 northern hemisphere season surface antigen inactivated trivalent influenza vaccine--Assessing the immunogenicity and safety in an open label, uncontrolled study.

    PubMed

    Roggelin, Louise; Vinnemeier, Christof D; Meyer, Seetha; Witte, Kai; Marx, Lydia; Theeß, Wiebke; Burchard, Gerd D; Rolling, Thierry; Cramer, Jakob P

    2015-01-01

    The present study evaluated the safety and immunogenicity of the 2013/2014 trivalent surface antigen inactivated subunit seasonal influenza virus vaccine Fluvirin® in healthy adults (18 - ≤ 60 years) and elderly (>60 years). The vaccine contained 15 µg haemagglutinin protein from each of influenza A/California/7/2009 (H1N1)pdm09-like strain, A/Victoria/361/2011 (H3N2)-like strain and B/Massachusetts/2/2012-like strain (B/Yamagata) as recommended by the WHO in the 2013/2014 Northern Hemisphere season. Antibody response to each influenza antigen after vaccination was measured prior to vaccination and 21 d after by single radial hemolysis (SRH) assay or hemagglutination inhibition (HI) assay in accordance with Guidance CPMP/BWP/214/96. 125 subjects (61 adults and 64 elderly) were enrolled in the study. Pre-vaccination protective antibody levels (SRH area ≥ 25 mm(2)) against A(H1N1), A(H3N2) and the B strain were detected in 17%, 20% and 57% of adults and in 36%, 20% and 55% of elderly, respectively, Post-vaccination, SRH area ≥ 25 mm(2) was detectable in 95%, 82% and 92% in adult and in 80%, 84% and 92% of the elderly subjects for A(H1N1), A(H3N2) and the B strain, respectively. Geometric mean ratio (GMR) was higher in adult subjects (2.62-7.62) than in elderly subjects (2.33-3.42). All three CHMP licensure criteria were met for all strains contained in the vaccine for both age groups. The most frequently reported solicited local and systemic reactions were pain at the injection side, headache and fatigue. In conclusion, the vaccine demonstrated a good immunogenicity and an acceptable safety profile in both adults and elderly.

  18. A multicenter, open-label phase II study of recombinant CPT (Circularly Permuted TRAIL) plus thalidomide in patients with relapsed and refractory multiple myeloma.

    PubMed

    Geng, Chuanying; Hou, Jian; Zhao, Yaozhong; Ke, Xiaoyan; Wang, Zhao; Qiu, Lugui; Xi, Hao; Wang, Fuxu; Wei, Na; Liu, Yan; Yang, Shifang; Wei, Peng; Zheng, Xiangjun; Huang, Zhongxia; Zhu, Bing; Chen, Wen-Ming

    2014-11-01

    Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a novel antitumor candidate for multiple myeloma (MM) and other hematologic malignancies. In this phase II study, the safety and efficacy of CPT plus thalidomide was investigated in thalidomide-resistant MM patients. A total of 43 patients were recruited into three CPT plus thalidomide cohorts based on CPT dosage in sequence: 5 mg/kg (n = 11), 8 mg/kg (n = 17), and 10 mg/kg (n = 15). CPT was administered via intravenous infusion on days 1-5, and thalidomide was given orally at 100 mg once daily in each 21-day cycle. The overall response rate (ORR) of 41 efficacy-evaluable patients was 22.0% (2 complete response, 3 near complete response, and 4 partial response). No significant difference in the ORR was observed among the three dose cohorts; however, the ORR tended to be higher with the higher-dose regimen. Median progression-free survival and median duration of response were 6.6 months and 6.1 months, respectively. The most common treatment-related adverse events (TRAEs) were neutropenia (46.5%), leukopenia (41.9%), fever (37.2%), elevated AST (32.6%), and elevated ALT (20.9%). TRAEs of Grade 3-4 were mainly neutropenia (18.6%), anemia (9.3%), elevated AST (7.0%), and leukopenia (4.7%). No significant differences were found in the incidence and severity of TRAEs among the three cohorts. In conclusion, CPT plus thalidomide was well tolerated with no occurrence of dose-limiting toxicities and demonstrated promising antitumor activity in RRMM patients. CPT at 10 mg/kg for 5 days in combination with thalidomide and dexamethason will be studied in the next clinical trial.

  19. Randomized open-label pilot study of the influence of probiotics and the gut microbiome on toxic metal levels in Tanzanian pregnant women and school children.

    PubMed

    Bisanz, Jordan E; Enos, Megan K; Mwanga, Joseph R; Changalucha, John; Burton, Jeremy P; Gloor, Gregory B; Reid, Gregor

    2014-10-07

    Exposure to environmental toxins is a 21st century global health problem that is often the result of dietary intake. Although efforts are made to reduce dietary toxin levels, they are often unsuccessful, warranting research into novel methods to reduce host exposure. Food-grade microbes that can be delivered to the gastrointestinal tract and that are capable of sequestering toxins present a safe and cost-effective intervention. We sought to investigate the potential for probiotic-supplemented yogurt to lower heavy metal levels in at-risk populations of pregnant women and in children in Mwanza, Tanzania, and to examine the microbiome in relation to toxin levels. Two populations suspected to have high toxic metal exposures were studied. A group of 44 school-aged children was followed over 25 days, and 60 pregnant women were followed over their last two trimesters until birth. A yogurt containing 10(10) CFU Lactobacillus rhamnosus GR-1 per 250 g was administered, while control groups received either whole milk or no intervention. Changes in blood metal levels were assessed, and the gut microbiomes of the children were profiled by analyzing 16S rRNA sequencing via the Ion Torrent platform. The children and pregnant women in the study were found to have elevated blood levels of lead and mercury compared to age- and sex-matched Canadians. Consumption of probiotic yogurt had a protective effect against further increases in mercury (3.2 nmol/liter; P = 0.035) and arsenic (2.3 nmol/liter; P = 0.011) blood levels in the pregnant women, but this trend was not statistically significant in the children. Elevated blood lead was associated with increases in Succinivibrionaceae and Gammaproteobacteria relative abundance levels in stool. Importance: Probiotic food produced locally represents a nutritious and affordable means for people in some developing countries to counter exposures to toxic metals. Further research and field trials are warranted to explore this approach in

  20. Phase 1/2 open-label dose-escalation study of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with painful diabetic peripheral neuropathy.

    PubMed

    Ajroud-Driss, Senda; Christiansen, Mark; Allen, Jeffrey A; Kessler, John A

    2013-06-01

    This study aimed to evaluate the safety and preliminary efficacy of intramuscular injections of plasmid DNA (VM202) expressing two isoforms of hepatocyte growth factor (HGF) in subjects with painful diabetic peripheral neuropathy (PDPN). Twelve patients in three cohorts (4, 8, and 16 mg) received two sets of VM202 injections separated by two weeks. Safety and tolerability were evaluated and the visual analog scale (VAS), the short form McGill questionnaire (SF-MPQ), and the brief pain inventory for patients with diabetic peripheral neuropathy (BPI-DPN) measured pain level throughout 12 months after treatment. No serious adverse events (AEs) were observed. The mean VAS was reduced from baseline by 47.2% (P = 0.002) at 6 months and by 44.1% (P = 0.005) at 12 months after treatment. The VAS scores for the 4, 8, and 16 mg dose cohorts at 6 months follow-up decreased in a dose-responsive manner, by 21% (P = 0.971), 53% (P = 0.014), and 62% (P = 0.001), respectively. The results with the BPI-DPN and SF-MPQ showed patterns similar to the VAS scores. In conclusion, VM202 treatment appeared to be safe, well tolerated, and sufficient to provide long term symptomatic relief and improvement in the quality of life in patients with PDPN. PMID:23609019

  1. Phase 1/2 Open-label Dose-escalation Study of Plasmid DNA Expressing Two Isoforms of Hepatocyte Growth Factor in Patients With Painful Diabetic Peripheral Neuropathy

    PubMed Central

    Ajroud-Driss, Senda; Christiansen, Mark; Allen, Jeffrey A; Kessler, John A

    2013-01-01

    This study aimed to evaluate the safety and preliminary efficacy of intramuscular injections of plasmid DNA (VM202) expressing two isoforms of hepatocyte growth factor (HGF) in subjects with painful diabetic peripheral neuropathy (PDPN). Twelve patients in three cohorts (4, 8, and 16 mg) received two sets of VM202 injections separated by two weeks. Safety and tolerability were evaluated and the visual analog scale (VAS), the short form McGill questionnaire (SF-MPQ), and the brief pain inventory for patients with diabetic peripheral neuropathy (BPI-DPN) measured pain level throughout 12 months after treatment. No serious adverse events (AEs) were observed. The mean VAS was reduced from baseline by 47.2% (P = 0.002) at 6 months and by 44.1% (P = 0.005) at 12 months after treatment. The VAS scores for the 4, 8, and 16 mg dose cohorts at 6 months follow-up decreased in a dose–responsive manner, by 21% (P = 0.971), 53% (P = 0.014), and 62% (P = 0.001), respectively. The results with the BPI-DPN and SF-MPQ showed patterns similar to the VAS scores. In conclusion, VM202 treatment appeared to be safe, well tolerated, and sufficient to provide long term symptomatic relief and improvement in the quality of life in patients with PDPN. PMID:23609019

  2. A 12-month, open-label, comparative study of quetiapine and risperidone in the acute and long-term treatment of schizophrenia.

    PubMed

    Perez, Victor; Cañas, Fernando; Tafalla, Monica

    2008-05-01

    This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.

  3. Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study

    PubMed Central

    Rorie, David A; Rogers, Amy; Mackenzie, Isla S; Ford, Ian; Webb, David J; Willams, Bryan; Brown, Morris; Poulter, Neil; Findlay, Evelyn; Saywood, Wendy; MacDonald, Thomas M

    2016-01-01

    Introduction Nocturnal blood pressure (BP) appears to be a better predictor of cardiovascular outcome than daytime BP. The BP lowering effects of most antihypertensive therapies are often greater in the first 12 h compared to the next 12 h. The Treatment In Morning versus Evening (TIME) study aims to establish whether evening dosing is more cardioprotective than morning dosing. Methods and analysis The TIME study uses the prospective, randomised, open-label, blinded end-point (PROBE) design. TIME recruits participants by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. Participants must be aged over 18 years, prescribed at least one antihypertensive drug taken once a day, and have a valid email address. After the participants have self-enrolled and consented on the secure TIME website (http://www.timestudy.co.uk) they are randomised to take their antihypertensive medication in the morning or the evening. Participant follow-ups are conducted after 1 month and then every 3 months by automated email. The trial is expected to run for 5 years, randomising 10 269 participants, with average participant follow-up being 4 years. The primary end point is hospitalisation for the composite end point of non-fatal myocardial infarction (MI), non-fatal stroke (cerebrovascular accident; CVA) or any vascular death determined by record-linkage. Secondary end points are: each component of the primary end point, hospitalisation for non-fatal stroke, hospitalisation for non-fatal MI, cardiovascular death, all-cause mortality, hospitalisation or death from congestive heart failure. The primary outcome will be a comparison of time to first event comparing morning versus evening dosing using an intention-to-treat analysis. The sample size is calculated for a two-sided test to detect 20% superiority at 80% power. Ethics and dissemination TIME has ethical approval in the UK, and results will be published in a

  4. Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: a randomized, open-label, multicentre, allopurinol-controlled study

    PubMed Central

    Yu, K-H; Lai, J-H; Hsu, P-N; Chen, D-Y; Chen, C-J; Lin, H-Y

    2016-01-01

    Objectives: This phase IIIB study compared the efficacy and safety of febuxostat and allopurinol in gout patients with or without tophi who were HLA-B*5801 negative. Method: Eligible patients were randomized to a febuxostat group (80 mg QD) or an allopurinol group (300 mg QD). Following an initial 2-week washout period, over the next 12 weeks we made five measurements of serum urate levels along with assessments of adverse events (AEs). Results: Forty-three out of 152 screened subjects (28.3%) were ineligible either because of the presence of the HLA-B*5801 allele or for various other reasons. The febuxostat group (n = 54) and the allopurinol group (n = 55) had no significant differences in demographic or baseline characteristics. From week 2 to week 12, the febuxostat group had a significantly lower serum urate level than the allopurinol group (p ≤ 0.001 for all comparisons) and significantly more patients with serum urate levels less than 6.0 mg/dL. The serum urate levels of the febuxostat group declined by more than 40% from week 2 to week 12 and this decrease was greater than that in the allopurinol group (~30%). The two groups were similar in terms of AEs. Conclusions: Febuxostat was more effective than allopurinol in reducing the serum urate levels of Han Chinese patients with gout or tophaceous gout who were HLA-B*5801 negative, without causing any serious skin reactions. Febuxostat should be considered for treatment of Han Chinese patients with gout who are HLA-B*5801 negative. PMID:26771445

  5. Absorption, Distribution, and Excretion of the Investigational Agent Orteronel (TAK-700) in Healthy Male Subjects: A Phase 1, Open-Label, Single-Dose Study.

    PubMed

    Suri, Ajit; Pusalkar, Sandeepraj; Li, Yuexian; Prakash, Shimoga

    2016-05-01

    This study evaluated the absorption, distribution, and excretion of orteronel, an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. Six healthy male subjects received a single 400-mg dose of radiolabeled [(14) C]-orteronel (18.5 kBq). The pharmacokinetics of [(14) C]-radioactivity, orteronel, and the primary metabolite M-I were characterized by ultra-performance liquid chromatography-tandem mass spectrometry, and mass balance recovery of [(14) C]-radioactivity was determined by liquid scintillation counting and accelerator mass spectrometry. Median time to maximum observed concentration of [(14) C]-radioactivity was 2.5 hours (plasma/whole blood) and of orteronel was 1 hour (plasma). Mean terminal half-life for [(14) C]-radioactivity in plasma and whole blood was 9.46 and 7.39 hours, respectively. For [(14) C]-radioactivity, the geometric mean whole blood-to-plasma ratios for maximum observed plasma/whole-blood concentration, area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUC0-last ), and AUC0-inf (AUC from time 0 to infinity) were 1.04, 0.92, and 0.93, respectively. Dose recovery accounted for 95.9% of the administered orteronel dose; the majority of excretion occurred by 96 hours postdose. The principal excretion route was via urine (mean, 77.5%; including 49.7% unchanged drug and 16.3% M-I) compared with 18.4% via feces. Three mild adverse events were reported; none were considered serious or related to orteronel. PMID:27163496

  6. Erlotinib plus capecitabine as first-line treatment for older Chinese patients with advanced adenocarcinoma of the lung (C-TONG0807): an open-label, single arm, multicenter phase II study.

    PubMed

    Zhao, Hong-Yun; Chen, Gong-Yan; Huang, Yan; Li, Xiao-li; Feng, Ji-Feng; Shi, Mei-Qi; Cheng, Ying; Ma, Li-Xia; Zhang, Yi-Ping; Gu, Cui-Ping; Song, Xiang-Qun; Zhou, Da; Zhang, Li

    2015-01-01

    Preclinical studies have shown synergism between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and antifolates in solid tumors. This study is to investigate the efficacy and tolerability of erlotinib plus capecitabine as first-line treatment in older Chinese patients (≥ 65 years) with lung adenocarcinoma. This is an open-label, single arm, multicenter phase II clinical trial. Sixty- two patients with previously untreated stage IIIB/IV adenocarcinoma and age 65 years or above were enrolled at four tertiary teaching hospitals and 2 provincial hospitals in China; 58 patients fulfilled the study requirements. Erlotinib (150 mg/day) and capecitabine (1000 mg/m2 twice daily on days 1-14) were administered during every 21-day cycle. The primary endpoint was the non-progression rate at 12 weeks. EGFR and K-ras mutation rates were determined using PCR. Tumor expression of different biomarkers was assessed using immunohistochemistry. In a cohort of 58 patients, 34 patients had no disease progression at 12 weeks following treatment. The objective response rate was 29.3%, and the disease control rate was 75.9%. The objective response rate was significantly higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with thymidine phosphorylase-negative tumors had significantly longer overall survival after one year than patients with thymidine phosphorylase-positive tumors. Forty-four patients had at least one primary adverse events (AEs), including skin rash (n = 30), grade 3 AEs (n = 17), and grade 4 AEs (n = 7). This is the first phase II clinical trial to assess erlotinib plus capecitabine combination therapy as first-line treatment in older patients with lung adenocarcinoma. Erlotinib/capecitabine chemotherapy was significantly better in patients with EGFR mutations and in those with thymidine phosphorylase-negative tumors. The use of fluorouracil derivatives for the treatment of lung adenocarcinoma warrants further study.

  7. A multiple-dose, open-label, safety, compliance, and usage evaluation study of epicutaneously applied Diractin (ketoprofen in Transfersome) in joint/musculoskeletal pain or soft tissue inflammation.

    PubMed

    Kneer, Werner; Rother, Ilka; Rother, Matthias; Seidel, Egbert

    2009-01-01

    The risk of oral NSAID including Cox-2 inhibitors to cause gastrointestinal, renal or cardiovascular adverse events related to systemic drug exposure could be reduced by local application. But only few long-term studies have been published to show safety and efficacy for long-term use of topical NSAID s. Diractin (formerly IDEA-033) is a viscous, aqueous formulation for epicutaneous application of ketoprofen based on ultra-deformable, self-regulating carrier (Transfersome). This multiple-dose, open label study with treatment periods up to 18 months included 402 patients with joint pain, musculoskeletal pain, stiffness or soft tissue inflammation (age of 61.4+/-11.5 years). Most of the patients suffered from osteoarthritis (OA) of the knee (68.9%). Diractin was applied epicutaneously up to twice daily with a maximum dose of 220 mg ketoprofen per a maximum of 2 application sites. The mean pain score at baseline was 5.4+/-.4 on a 10 point categorical scale. During the study the pain score progressively improved up to week 36 (3.5+/-1.9) without a substantial further change during the rest of observation period of up to 18 months. The reduction of pain scores between week 0 (baseline) and at all later visits was statistically significant (P<0.0001). Patients also reported an improvement of quality of life on the EUROQoL. The majority of treatment related adverse events were skin and subcutaneous tissue disorders with the highest frequency reported for erythema (16.7%) and pruritus (2.0%). Systemic ketoprofen exposure remained low throughout the study period with plasma concentrations of less than 1% of what was reported for a single, standard oral dose of 200 mg ketoprofen. There were no occurrences of treatment related serious adverse events and no remarkable changes in laboratory values or vital signs. In summary, Diractin provided adequate pain relief with a good safety and tolerability profile when used for up to 18 months (72 weeks).

  8. Open-label, Prospective, Investigator Initiated Study to Assess the Clinical Role of Oral Natural or Synthetic Progesterone During Stimulated IUI Cycles for Unexplained Infertility

    PubMed Central

    Malhotra, Jaideep

    2016-01-01

    Background Unexplained infertility remains as one of the important subtype of infertility that follows expectant management with Intrauterine Insemination (IUI) in most cases. Aim To evaluate the clinical role of progesterone supplement as luteal phase support for women with unexplained infertility following stimulation protocol with Clomiphene Citrate (CC)/Human Menopausal Gonadotropin (HMG). Materials and Methods An investigator initiated study to survey the success rate for first cycle of IUI following stimulation protocol with CC/HMG & luteal phase support with oral natural or synthetic progesterone was conducted. 120 patient records between observation period of Jan to May ’14 were retrieved especially for subjects undergoing IUI procedure for Unexplained infertility. Patients with baseline Serum (Sr). progesterone records who received Oral Natural Micronized Progesterone Sustained Release (Oral NMP SR) (N=45) or Dydrogesterone (n=33) following CC/HMG induction protocol and human Chorionic Gonadotropin(HCG) Inj., were further analysed following Luteal Phase Support(LPS) with oral natural or synthetic progesterone. Results Baseline demographics showed 78 patients with mean age, weight and cycle duration of 29.5 yrs, 57.3 kg & 28.6 days respectively. Progesterone was supplemented as Oral NMP SR 200/300 mg OD or Dydrogesterone 10 mg bid in 22, 23 and 33 patients respectively. In all cases ovulation was triggered with HCG inj., followed by IUI within the next 48 hours while baseline sr. progesterone levels were being assessed. Medicines and Healthcare Products Regulatory Agency (MHRA) UK recommended therapeutic compliance to suggest sr. progesterone levels of ≥14ng/ml were recorded as Mid-luteal levels in all of these patients. This therapeutic compliance was noted in 82.2% & 78.8% of the patients treated with oral NMP SR or Dydrogesterone respectively. Pregnancy was observed amongst 5 and 10 patients treated with oral NMP SR and Dydrogesterone respectively at

  9. Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study

    PubMed Central

    2012-01-01

    Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of bone and cartilage. Although its etiology is unknown, the hydroxyl radical has been suggested to be involved in the pathogenesis of RA. Recently, molecular hydrogen (H2) was demonstrated to be a selective scavenger for the hydroxyl radical. Also, the method to prepare water containing extremely high concentration of H2 has been developed. We hypothesized that H2 in the water could complement conventional therapy by reducing the oxidative stress in RA. Methods Twenty patients with rheumatoid arthritis (RA) drank 530 ml of water containing 4 to 5 ppm molecular hydrogen (high H2 water) every day for 4 weeks. After a 4-week wash-out period, the patients drank the high H2 water for another 4 weeks. Urinary 8-hydroxydeoxyguanine (8-OHdG) and disease activity (DAS28, using C-reactive protein [CRP] levels) was estimated at the end of each 4-week period. Results Drinking high H2 water seems to raise the concentration of H2 more than the H2 saturated (1.6 ppm) water in vivo. Urinary 8-OHdG was significantly reduced by 14.3% (p < 0.01) on average. DAS28 also decreased from 3.83 to 3.02 (p < 0.01) during the same period. After the wash-out period, both the urinary 8-OHdG and the mean DAS28 decreased, compared to the end of the drinking period. During the second drinking period, the mean DAS28 was reduced from 2.83 to 2.26 (p < 0.01). Urinary 8-OHdG was not further reduced but remained below the baseline value. All the 5 patients with early RA (duration < 12 months) who did not show antibodies against cyclic citrullinated peptides (ACPAs) achieved remission, and 4 of them became symptom-free at the end of the study. Conclusions The results suggest that the hydroxyl radical scavenger H2 effectively reduces oxidative stress in patients with this condition. The symptoms of RA were significantly improved with high H2 water. PMID:23031079

  10. SmartPill® as an objective parameter for determination of severity and duration of postoperative ileus: study protocol of a prospective, two-arm, open-label trial (the PIDuSA study)

    PubMed Central

    Vilz, Tim O; Pantelis, Dimitrios; Lingohr, Philipp; Fimmers, Rolf; Esmann, Anke; Randau, Thomas; Kalff, Jörg C; Coenen, Martin; Wehner, Sven

    2016-01-01

    Introduction Postoperative ileus (POI) is a frequent complication after abdominal surgery (AS). Until today, neither a prophylaxis nor an evidence-based therapy exists. This originates from the absence of objective parameters evaluating the severity and duration of POI resulting in clinical trials of modest quality. The SmartPill®, a capsule which frequently measures pH value, temperature and intraluminal pressure after swallowing, offers an elegant option for analysing gastrointestinal (GI) transit times and smooth muscle activity in vivo. As the use in patients in the first months after AS is not covered by the marketing authorisation, we aim to investigate the safety and feasibility of the SmartPill® immediately after surgery. Additionally, we analyse the influence of prokinetics and laxatives as well as standardised physiotherapy on postoperative bowel contractility, as scientific evidence of its effects is still lacking. Methods and analysis The PIDuSA study is a prospective, single-centre, two-arm, open-label trial. The SmartPill® will be applied to 55 patients undergoing AS having a high risk for POI and 10 patients undergoing extra-abdominal surgery rarely developing POI. The primary objective is the safety of the SmartPill® in patients after surgery on the basis of adverse device effects/serious adverse device effects (ADE/SADE). The sample size suggests that events with a probability of 3% could be seen with a certainty of 80% for at least once in the sample. Secondary objective is the analysis of postoperative intestinal activity in the GI tract in both groups. Furthermore, clinical signs of bowel motility disorders will be correlated to the data measured by the SmartPill® to evaluate its significance as an objective parameter for assessing POI severity. Additionally, effects of prokinetics, laxatives and physiotherapy on postoperative peristaltic activity recorded by the SmartPill® will be analysed. Ethics and dissemination The protocol was

  11. Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study

    PubMed Central

    Pozniak, Anton; Arribas, Jose R.; Gathe, Joseph; Gupta, Samir K.; Post, Frank A.; Bloch, Mark; Avihingsanon, Anchalee; Crofoot, Gordon; Benson, Paul; Lichtenstein, Kenneth; Ramgopal, Moti; Chetchotisakd, Ploenchan; Custodio, Joseph M.; Abram, Michael E.; Wei, Xuelian; Cheng, Andrew; McCallister, Scott; SenGupta, Devi

    2016-01-01

    Background: Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved renal and bone safety compared with TDF-containing regimens. We report the 48 week safety and efficacy of a once-daily single tablet regimen of elvitegravir 150 mg (E), cobicistat 150 mg (C), emtricitabine 200 mg (F), and TAF 10 mg (E/C/F/TAF) in HIV-1-infected patients with mild to moderate renal impairment. Methods: We enrolled virologically suppressed HIV-1-infected subjects with estimated creatinine clearance (CrCl) 30–69 mL/min in a single-arm, open-label study to switch regimens to E/C/F/TAF. The primary endpoint was the change from baseline in glomerular filtration rate estimated using various formulae. This study is registered with ClinicalTrials.gov, number NCT01818596. Findings: We enrolled and treated 242 patients with mean age 58 years, 18% Black, 39% hypertension, 14% diabetes. Through week 48, no significant change in estimated CrCl was observed. Two patients (0.8%) discontinued study drug for decreased creatinine clearance, neither had evidence of renal tubulopathy and both had uncontrolled hypertension. Subjects had significant improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001 for all). Hip and spine bone mineral density significantly increased from baseline to week 48 (mean percent change +1.47 and +2.29, respectively, P < 0.05). Ninety-two percent (222 patients) maintained HIV-1 RNA <50 copies per milliliter at week 48. Interpretation: Switch to E/C/F/TAF was associated with minimal change in GFR. Proteinuria, albuminuria and bone mineral density significantly improved. These data support the efficacy and safety of once daily E/C/F/TAF in HIV+ patients with mild or moderate renal impairment without dose adjustment. PMID:26627107

  12. Comparative evaluation of efficacy and safety of combination of metformin-vidagliptin versus metfromin-glimepiride in most frequently used doses in patients of type 2 diabetes mellitus with inadequately controlled metformin monotherapy-A randomised open label study

    PubMed Central

    Gupta, Shallini; Khajuria, Vijay; Tandon, Vishal R.; Mahajan, Annil; Gillani, Zahid H.

    2015-01-01

    Aim and Objective: The aim was to evaluate and compare the efficacy and safety of combinations of metformin-vidagliptin (MF-VG) and metfromin-glimepiride (MF-GP) in type 2 diabetes mellitus (T2DM) patients. Materials and Methods: A comparative randomized open-label trial was conducted on patients with uncomplicated T2DM, on treatment with MF for 4 months out of which on maximum tolerated dose of MF (1000-2500 mg/day) for 4 weeks, glycosylated Haemoglobin [HbA1c]) ≥6.5%, fasting blood glucose (FBG) ≥126 mg/dl and post prandial glucose (PPG) ≥200 mg/dl were included in the study. Patients were randomized to receive MF (500 mg BD) + VG (50 mg BD) or MF (500 mg BD) + GP (2 mg BD). Results: Both the groups caused significant decline in blood glucose levels both FBG as well as PPG levels (P < 0.01). HbA1c was also reduced significantly in both groups at 12 weeks (P < 0.01). Total serum cholesterol, triglycerides, low-density lipoprotein and very low-density lipoprotein decreased significantly, whereas high-density lipoprotein levels increased significantly from baseline levels in both the groups (P < 0.01). Intergroup comparison failed to demonstrate any statistical difference on all of above parameters. Both weight and body mass index did not alter statistically from baseline in either of the groups as well as demonstrated no difference statistically on comparison (P > 0.05). At the end of the study, both liver functions tests and renal functions tests remained unaltered statistically and within normal clinical range in both the groups (P > 0.05). However, hypoglycemia and other adverse events were numerically more in MF + GP group. Conclusion: Both the regimens on comparison revealed similar efficacy and safety thereby failing to prove superiority over each other. PMID:26229753

  13. A 4-month, open-label study evaluating the efficacy of eflornithine 11.5% cream in the treatment of unwanted facial hair in women using TrichoScan.

    PubMed

    Hoffmann, Rolf

    2008-01-01

    Eflornithine 11.5% cream is an effective treatment for unwanted facial hair (UFH) in women with the effect on facial hair growth starting to be seen from 1 month after treatment initiation. TrichoScan is a validated method of assessing hair length, thickness, density, and growth rate using contact skin microscopy. The study aimed to evaluate the efficacy of eflornithine cream in women with UFH, as assessed by TrichoScan. In this open-label, single-centre study, 25 women (aged 25-63 years) applied eflornithine 11.5% cream to the upper lip twice daily for 4 months. Hair density, mean and cumulative hair length, mean hair thickness and hair growth rate were assessed at baseline and Month 1, 2 and 4 using TrichoScan. Eflornithine cream significantly decreased hair density from baseline to Month 1 (- 11.4 hairs/cm2, p = 0.014), Month 2 (- 16.5 hairs/cm2, p = 0.013) and Month 4 (- 12.05 hairs/cm2, p = 0.05). In addition, cumulative hair length decreased from baseline to Month 1 (- 7.104 mm, p = 0.001), Month 2 (- 10.054 mm, p < 0.001) and Month 4 (- 8.061 mm, p = 0.001). There was also a significant decrease in hair growth rate. Mean hair thickness did not change significantly. Eflornithine 11.5% cream is an effective treatment for UFH in women with the effect on facial hair growth starting to be seen from 1 month after treatment initiation.

  14. An open-label, multicenter, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in Chinese men naïve to phosphodiesterase 5 inhibitor therapy

    PubMed Central

    Bai, Wen-Jun; Li, Hong-Jun; Dai, Yu-Tian; He, Xue-You; Huang, Yi-Ran; Liu, Ji-Hong; Sorsaburu, Sebastian; Ji, Chen; Jin, Jian-Jun; Wang, Xiao-Feng

    2015-01-01

    The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in Chinese men naïve to phosphodiesterase 5 (PDE5) inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire (PITPQ). Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function (IIEF) erectile function (EF) domain, sexual encounter profile (SEP) Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men (91%) completed the randomized treatment phase. Two hundred and forty-two per 350 (69.1%) patients preferred 20-mg tadalafil, and 108/350 (30.9%) preferred 100-mg sildenafil (P < 0.001) as their treatment in the 8 weeks extension. Ninety-two per 242 (38%) patients strongly preferred tadalafil and 37/108 (34.3%) strongly the preferred sildenafil. The SEP2 (penetration), SEP3 (successful intercourse), and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by > 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED naïve to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe. PMID:25370206

  15. Efficacy and safety of canagliflozin alone or as add-on to other oral antihyperglycemic drugs in Japanese patients with type 2 diabetes: A 52-week open-label study

    PubMed Central

    Inagaki, Nobuya; Kondo, Kazuoki; Yoshinari, Toru; Kuki, Hideki

    2015-01-01

    Aims/Introduction Canagliflozin is a sodium–glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes. Our aim was to examine its efficacy and safety as monotherapy or in combination with commonly used oral antihyperglycemic drugs in Japanese patients with type 2 diabetes. Materials and Methods Patients on diet/exercise alone or diet/exercise plus an oral antihyperglycemic drug (sulfonylurea, glinide, α-glucosidase inhibitor, biguanide, thiazolidinedione or dipeptidyl peptidase-4 inhibitor) were randomized to either 100 or 200 mg canagliflozin while continuing prior therapy. Patients were treated for 52 weeks in an open-label manner. Results Canagliflozin significantly reduced hemoglobin A1c, fasting plasma glucose and bodyweight in all the study groups. Improvements were apparent by 4 weeks of treatment, and were maintained for 52 weeks. The reduction in hemoglobin A1c ranged from −0.80 to −1.06%, and from −0.93 to −1.26% in the 100 and 200 mg canagliflozin groups, respectively. Drug-related adverse events occurred in approximately one-third of patients, and included hypoglycemia/asymptomatic hypoglycemia and pollakiuria. Hypoglycemia/asymptomatic hypoglycemia was most common in patients treated with a sulfonylurea. Most adverse events were classified as mild or moderate in severity. Conclusions The results of the present study confirmed that treatment with canagliflozin resulted in significant reductions in glycemic control and bodyweight that were maintained for 52 weeks of treatment irrespective of whether it was administered as monotherapy or in combination with another oral antihyperglycemic drug. Canagliflozin was well tolerated, with a low incidence of drug-related adverse events. This trial was registered with ClinicalTrials.gov (no. NCT01387737). PMID:25802729

  16. Immunogenicity, Safety, and Tolerability of 13-Valent Pneumococcal Conjugate Vaccine Followed by 23-Valent Pneumococcal Polysaccharide Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant Aged ≥2 Years: An Open-Label Study

    PubMed Central

    Cordonnier, Catherine; Ljungman, Per; Juergens, Christine; Maertens, Johan; Selleslag, Dominik; Sundaraiyer, Vani; Giardina, Peter C.; Clarke, Keri; Gruber, William C.; Scott, Daniel A.; Schmoele-Thoma, Beate

    2015-01-01

    Background. Life-threatening Streptococcus pneumoniae infections often occur after hematopoietic stem cell transplant (HSCT); vaccination is important for prevention. Methods. In an open-label study, patients (n = 251) 3–6 months after allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity at prespecified time points and vaccine safety were assessed. Results. In the evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from baseline to postdose 3 showed significant increases in antibody levels across all PCV13 serotypes (GMFR range, 2.99–23.85; 95% confidence interval lower limit, >1); there were significant declines over the next 6 months, significant increases from predose 4 to postdose 4 (GMFR range, 3.00–6.97), and little change after PPSV23 (GMFR range, 0.86–1.12). Local and systemic reactions were more frequent after dose 4. Six patients experienced serious adverse events possibly related to PCV13 (facial diplegia, injection-site erythema and pyrexia, autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3 leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barré syndrome), or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines. Conclusions. A 3-dose PCV13 regimen followed by a booster dose may be required to protect against pneumococcal disease in HSCT recipients. Dose 4 was associated with increased local and systemic reactions, but the overall safety profile of a 4-dose regimen was considered acceptable. Clinical Trials Registration. NCT00980655. PMID:25870329

  17. Effect of levitra on sustenance of erection (EROS): an open-label, prospective, multicenter, single-arm study to investigate erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction.

    PubMed

    Shin, Y S; Lee, S W; Park, K; Chung, W S; Kim, S W; Hyun, J S; Moon, D G; Yang, S-K; Ryu, J K; Yang, D Y; Moon, K H; Min, K S; Park, J K

    2015-01-01

    To investigate the change of erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction (ED). Effect of levitra on sustenance of erection was an open-label, prospective, multicenter and single-arm study designed to measure the duration of erection in men with ED receiving a flexible dose of vardenafil over an 8-week treatment period. Patients were instructed to take vardenafil 10 mg 60 min before attempting the intercourse. Vardenfil could be increased to 20 mg or decreased to 5 mg concerning patients' efficacy and safety. Following the initial screening, patients entered a 4-week treatment-free run-in phase and 8-week treatment period, during which they were instructed to attempt intercourse at least four times on four separate days. A total of 95 men were enrolled in 10 centers. After the 8 weeks treatment, the mean duration of erection leading to successful intercourse was statistically superior when patients were treated with vardenafil. After an 8-week treatment, the duration of erection leading to successful intercourse was 9.39 min. There were significant benefits with vardenafil in all domains of International Index of Erectile Function. Secondary efficacy end points included success rate of penetration, maintaining erection, ejaculation and satisfaction were superior when patients were treated with vardenafil. There was a significant correlation between duration of erection with other sexual factors. Also partner's sexual satisfaction was increased with vardenafil. Most adverse events were mild or moderate in severity. Vardenafil was safe and well tolerated. Vardenafil therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED with female partner. PMID:25471318

  18. A multicenter, primary care-based, open-label study to identify behaviors related to prescription opioid misuse, abuse, and diversion in opioid-experienced patients with chronic moderate-to-severe pain

    PubMed Central

    Setnik, Beatrice; Roland, Carl L; Sommerville, Kenneth W; Pixton, Glenn C; Berke, Robert; Calkins, Anne; Goli, Veeraindar

    2015-01-01

    Objective To compare the investigator assessment of patient risk for prescription opioid misuse, abuse, and diversion with patient self-reports of these activities in a population with chronic pain. Methods As a secondary objective of an open-label, multicenter, primary care-based clinical study to evaluate the success of converting opioid-experienced patients with chronic pain to morphine sulfate with sequestered naltrexone hydrochloride, risk for misuse, abuse, and diversion was assessed using two nonvalidated questionnaires: one was completed by the investigator and another by the patient (Self-Reported Misuse, Abuse, and Diversion [SR-MAD]). In addition, the validated Current Opioid Misuse Measure (COMM) test and urine drug test were used. Results Of the 684 patients assessed by the investigators, 537 returned the self-assessment, SR-MAD. Most patients were assigned by the investigator as low risk for misuse (84.2%), abuse (89.3%), and diversion (94.3%). Of the patients who returned SR-MAD, 60% indicated having taken more opioids than prescribed and 10.9% reported chewing or crushing their opioids in the past. Of the patients who completed COMM, 40.6% were deemed as having aberrant behaviors. COMM results correlated with the risk levels from the investigator assessment. One-third of patients (33.8%) had at least one abnormal urine drug test result. Conclusion More research is needed to better understand the gap between the investigator assessment of potential risk for misuse, abuse, and diversion and the actual extent of these behaviors among patients with chronic pain. PMID:26185467

  19. Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): an open-label prospective study of time in treatment, dose, side-effects and comorbidity.

    PubMed

    Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsøyr, Ole; Haavik, Jan; Peleikis, Dawn E

    2014-12-01

    How to generalize from randomized placebo controlled trials of ADHD drug treatment in adults to 'real-world' clinical practice is intriguing. This open-labeled prospective observational study examined the effectiveness of long-term stimulant and non-stimulant medication in adult ADHD including dose, side-effects and comorbidity in a clinical setting. A specialized ADHD outpatient clinic gave previously non-medicated adults (n=250) with ADHD methylphenidate as first-line drug according to current guidelines. Patients who were non-tolerant or experiencing low efficacy were switched to amphetamine or atomoxetine. Primary outcomes were changes of ADHD-symptoms evaluated with the Adult ADHD Self-Report Scale (ASRS) and overall severity by the Global Assessment of Functioning (GAF). Secondary outcomes were measures of mental distress, and response on the Clinical-Global-Impressions-Improvement Scale. Data at baseline and follow-ups were compared in longitudinal mixed model analyses for time on-medication, dosage, comorbidity, and side-effects. As results, 232 patients (93%) completed examination at the 12 month endpoint, and 163 (70%) remained on medication. Compared with the patients who discontinued medication, those still on medication had greater percentage reduction in ASRS-scores (median 39%, versus 13%, P<0.001) and greater improvement of GAF (median 20% versus 4%, P<0.001) and secondary outcomes. Continued medication and higher cumulated doses showed significant associations to sustained improvement. Conversely, psychiatric comorbidity and side-effects were related to lower effectiveness and more frequent termination of medication. Taken together, one-year treatment with stimulants or atomoxetine was associated with a clinically significant reduction in ADHD symptoms and mental distress, and improvement of measured function. No serious adverse events were observed.

  20. Design and Rationale of the APELOT Trial: A Randomized, Open-Label, Multicenter, Phase IV Study to Evaluate the Antiplatelet Effect of Different Loading Dose of Ticagrelor in Patients With Non-ST Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

    PubMed

    Liu, Hui-Liang; Wei, Yu-Jie; Jin, Zhi-Geng; Zhang, Jiao; Ding, Peng; Yang, Sheng-Li; Luo, Jian-Ping; Ma, Dong-Xing; Liu, Ying; Han, Wei

    2016-05-01

    Ticagrelor is a direct acting on the P2Y12 receptor blocker, which provides faster and greater platelet inhibition than clopidogrel. However, several studies suggested that in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention (PCI), ticagrelor exhibits initial delay in the onset of antiplatelet action. Unlike ST-segment elevation myocardial infarction, in non-ST-segment elevation acute coronary syndrome (NSTE-ACS), management pathways are highly variable, and some patients may require surgery. Effect of higher loading dose (LD) of ticagrelor in patients with NSTE-ACS in providing faster and stronger inhibition of platelet aggregation is unknown and needs to be explored further.The AntiPlatelet Effect of different Loading dOse of Ticagrelor trial is an interventional, randomized, open-label, multicenter, phase IV trial designed to evaluate whether a high LD (360 mg) of ticagrelor compared with the conventional LD (180 mg) will result in a higher inhibition of platelet aggregation without increasing bleeding events in NSTE-ACS participants undergoing PCI.A total of 250 NSTE-ACS participants will be randomized to receive a ticagrelor LD (360 or 180 mg), followed by a maintenance dose of 90 mg twice a day (bid) starting 12 hours after the LD. The primary endpoint is platelet reactivity index measured by vasodilator-stimulated phosphoprotein phosphorylation 2 hours after the LD, and the secondary endpoints include occurrence of periprocedural myocardial infarction and bleeding events.The AntiPlatelet Effect of different Loading dOse of Ticagrelor trial will provide important information on the risks and benefits of a high LD (360 mg) of ticagrelor in achieving a faster and stronger platelet inhibition compared with the conventional LD (180 mg) in NSTE-ACS patients undergoing PCI. PMID:27258504

  1. A randomized open label study of pain medications (naproxen, acetaminophen and ibuprofen) for controlling side effects during initiation of IFN beta-1a therapy and during its ongoing use for relapsing-remitting multiple sclerosis.

    PubMed

    Leuschen, M Patricia; Filipi, Mary; Healey, Kathleen

    2004-12-01

    Multiple sclerosis (MS) patients initiating IFN beta-1a, Avonex, therapy (Group 1, n = 30) or experiencing side effects after 6 months on therapy (Group 2, n = 30) were randomized for 5 weeks open label adjunct therapy to naproxen (Aleve), acetaminophen (Tylenol) or ibuprofen (Advil). Our hypothesis was that non-prescription pain medications are effective in decreasing or alleviating the side effects associated with IFN beta-1a therapy. Contrary to the hypothesis, most patients in both groups continued to report side effects on all pain medications. After 5 weeks, headache, fever, chills and injection site pain were low in < or = 50% of patients. Moderate to significant fatigue, muscle or joint pain continued in most patients. As a quality of life measure, the Modified Fatigue Impact Scale (mFIS) improved for Group 1 on naproxen or ibuprofen with greatest improvement in physical subset (P = 0.002 for naproxen and P<0.01 for ibuprofen). Total mFIS for Group 1 on acetaminophen improved (P = 0.04) due to improved cognitive subset rather than physical subset. Group 2, with side effects initially, reported less significant fatigue (severity 5-10) but more moderate fatigue (severity 2-4) at study end for all three medications. All medications improved cognitive subset (P = 0.05). Physical mFIS subset did not improve for Group 2 on acetaminophen, but did with naproxen (P = 0.05) or ibuprofen (P = 0.03). Naproxen and ibuprofen were more effective than acetaminophen in minimizing physical side effects of IFN beta-1a. None of the three pain medications tested were as effective as hypothesized for minimizing fatigue or muscle and joint pain.

  2. Effect of levitra on sustenance of erection (EROS): an open-label, prospective, multicenter, single-arm study to investigate erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction.

    PubMed

    Shin, Y S; Lee, S W; Park, K; Chung, W S; Kim, S W; Hyun, J S; Moon, D G; Yang, S-K; Ryu, J K; Yang, D Y; Moon, K H; Min, K S; Park, J K

    2015-01-01

    To investigate the change of erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction (ED). Effect of levitra on sustenance of erection was an open-label, prospective, multicenter and single-arm study designed to measure the duration of erection in men with ED receiving a flexible dose of vardenafil over an 8-week treatment period. Patients were instructed to take vardenafil 10 mg 60 min before attempting the intercourse. Vardenfil could be increased to 20 mg or decreased to 5 mg concerning patients' efficacy and safety. Following the initial screening, patients entered a 4-week treatment-free run-in phase and 8-week treatment period, during which they were instructed to attempt intercourse at least four times on four separate days. A total of 95 men were enrolled in 10 centers. After the 8 weeks treatment, the mean duration of erection leading to successful intercourse was statistically superior when patients were treated with vardenafil. After an 8-week treatment, the duration of erection leading to successful intercourse was 9.39 min. There were significant benefits with vardenafil in all domains of International Index of Erectile Function. Secondary efficacy end points included success rate of penetration, maintaining erection, ejaculation and satisfaction were superior when patients were treated with vardenafil. There was a significant correlation between duration of erection with other sexual factors. Also partner's sexual satisfaction was increased with vardenafil. Most adverse events were mild or moderate in severity. Vardenafil was safe and well tolerated. Vardenafil therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED with female partner.

  3. Safety and tolerability of vortioxetine (15 and 20 mg) in patients with major depressive disorder: results of an open-label, flexible-dose, 52-week extension study

    PubMed Central

    Jacobsen, Paula L.; Harper, Linda; Chrones, Lambros; Chan, Serena

    2015-01-01

    Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10 mg/day vortioxetine for week 1, then adjusted between 15 and 20 mg for the remainder of the study, but not downtitrated below 15 mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery–Åsberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (Δ−4.2), the Clinical Global Impression Scale-Severity of Illness (Δ−1.2), and the Sheehan Disability Scale (Δ−4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20

  4. Open-Label Trial of Atomoxetine Hydrochloride in Adults with ADHD

    ERIC Educational Resources Information Center

    Johnson, Mats; Cederlund, Mats; Rastam, Maria; Areskoug, Bjorn; Gillberg, Christopher

    2010-01-01

    Background: While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Methods: Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Results: Ten patients met primary…

  5. Open-Label, Prospective Trial of Olanzapine in Adolescents with Subaverage Intelligence and Disruptive Behavioral Disorders

    ERIC Educational Resources Information Center

    Handen, Benjamin L.; Hardan, Antonio Y.

    2006-01-01

    Objective: Olanzapine, an atypical antipsychotic, has been shown to be efficacious for treatment of psychotic and mood disorders in adults. This prospective, open-label study was conducted to examine the safety and usefulness of olanzapine in treating disruptive behavior disorders in adolescents with subaverage intelligence. Method: Sixteen…

  6. An Open-Label Trial of Escitalopram in Pervasive Developmental Disorders.

    ERIC Educational Resources Information Center

    Owley, Thomas; Walton, Laura; Salt, Jeff; Guter, Stephen J., Jr.; Winnega, Marrea; Leventhal, Bennett L.; Cook, Edwin H., Jr.

    2005-01-01

    Objective: To assess the effect of escitalopram in the treatment of pervasive developmental disorders (PDDs). Method: This 10-week study had a forced titration, open-label design. Twenty-eight subjects (mean age 125.1 [+ or -] 33.5 months) with a PDD received escitalopram at a dose that increased weekly to a maximum dose of 20 mg as tolerated. The…

  7. Antihypertensive effect of barnidipine 10 mg or amlodipine 5 to 10 mg once daily in treatment-naive patients with essential hypertension: A 24-week, randomized, open-label, pilot study

    PubMed Central

    Rossetti, Giuseppe; Pizzocri, Samuele; Brasca, Francesco; Pozzi, Marta; Beltrami, Laura M.; Bolla, Giovanni B.; Famiani, Roberta; Caimi, Barbara; Omboni, Stefano; Magrini, Fabio; Carugo, Stefano

    2008-01-01

    Background: Dihydropyridine calcium antagonists are largely employed for the treatment of hypertension, coronary heart disease, and heart failure. Objective: The aim of our study was to compare the antihypertensive effect of the dihydropyridine calcium antagonists barnidipine and amlodipine. Methods: This was a 24-week, randomized, open-label, pilot study. Consecutive treatment-naive patients with grade I or II essential hypertension (office sitting systolic blood pressure [BP] of 140–179 mm Hg and diastolic BP of 90–109 mm Hg) were enrolled. The primary end points were the effect of treatment with either barnidipine 10 mg or amlodipine 5 mg once daily on office and ambulatory BP, left ventricular mass index (LVMI), and markers of cardiac damage, serum procollagen type I C-terminal propeptide, and plasma amino-terminal pro-B-type natriuretic peptide concentrations. Patients were assessed at enrollment, and 12 and 24 weeks. During each visit, the prevalence of adverse events (AEs) was also monitored using spontaneous reporting, patient interview, and physical examination, the relationship to study drug being determined by the investigators. Compliance with treatment was assessed at each study visit by counting returned tablets. Results: Thirty eligible patients (20 men, 10 women; mean [SD] age, 47 [12] years) were included in the study; all patients completed the 24 weeks of study treatment. Twelve weeks after randomization, 6 patients in the amlodipine group had their dose doubled to 10 mg due to inadequate BP control. Mean BP reductions at study end were not significantly different between the barnidipine and amlodipine groups (office BP, −10.3/−9.4 vs −16.6/−9.1 mm Hg; ambulatory BP, 9.4/6.4 vs 8.1/5.1 mm Hg). Reductions in LVMI and markers of cardiac damage were not significantly different between the 2 groups. Significantly more patients in the amlodipine group reported drug-related AEs compared with those in the barnidipine group (9 [60%] vs 2 [13

  8. Early intervention of long-acting nifedipine GITS reduces brachial–ankle pulse wave velocity and improves arterial stiffness in Chinese patients with mild hypertension: a 24-week, single-arm, open-label, prospective study

    PubMed Central

    Zhang, Jidong; Wang, Yan; Hu, Haijuan; Yang, Xiaohong; Tian, Zejun; Liu, Demin; Gu, Guoqiang; Zheng, Hongmei; Xie, Ruiqin; Cui, Wei

    2016-01-01

    Background Nifedipine gastrointestinal therapeutic system (GITS) is used to treat angina and hypertension. The authors aimed to study the early intervention impact on arterial stiffness and pulse wave velocity (PWV) independent of its blood-pressure-(BP) lowering effect in mild hypertensive patients. Methods This single-center, single-arm, open-label, prospective, Phase IV study recruited patients with mild hypertension and increased PWV from December 2013 to December 2014 (N=138; age, 18–75 years; systolic blood pressure, 140–160 mmHg; diastolic BP, 90–100 mmHg; increased brachial–ankle pulse wave velocity [baPWV, ≥12 m/s]). Nifedipine GITS (30 mg/d) was administered for 24 weeks to achieve target BP of <140/90 mmHg. The dose was uptitrated at 60 mg/d in case of unsatisfactory BP reduction after 4 weeks. Primary study end point was the change in baPWV after nifedipine GITS treatment. Hemodynamic parameters (office BP, 24-hour ambulatory BP monitoring, and heart rate and adverse events) were evaluated at baseline and followed-up at 2, 4, 8, 12, 18, and 24 weeks. Results Majority of patients (n=117; 84.8%) completed the study. baPWV decreased significantly at 4 weeks compared with baseline (1,598.87±239.82 vs 1,500.89±241.15 cm/s, P<0.001), was stable at 12 weeks (1,482.24±215.14 cm/s, P<0.001), and remained steady through 24 weeks (1,472.58±205.01 cm/s, P<0.001). Office BP reduced from baseline to week 4 (154/95 vs 136/85 mmHg) and remained steady until 24 weeks. Nifedipine GITS significantly decreased 24-hour ambulatory BP monitoring (P<0.001) after 24 weeks from baseline. Mean arterial pressure and pulse pressure were lowered significantly after 4, 12, and 24 weeks of treatment (P<0.001). These changes in baPWV were significantly correlated with changes in systolic blood pressure, diastolic BP, and mean arterial pressure (P<0.05), but not with changes in pulse pressure (P>0.05). There were no other drug-related serious adverse events. Conclusion

  9. An Open-label, Self-control, Prospective Study on Cognitive Function, Academic Performance, and Tolerability of Osmotic-release Oral System Methylphenidate in Children with Attention-deficit Hyperactivity Disorder

    PubMed Central

    Zheng, Yi; Liang, Jian-Min; Gao, Hong-Yun; Yang, Zhi-Wei; Jia, Fu-Jun; Liang, Yue-Zhu; Fang, Fang; Li, Rong; Xie, Sheng-Nan; Zhuo, Jian-Min

    2015-01-01

    Background: Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD. Methods: This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training. Results: A total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study. Conclusions: The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of

  10. Randomized, open-label, blinded-endpoint, crossover, single-dose study to compare the pharmacodynamics of torasemide-PR 10 mg, torasemide-IR 10 mg, and furosemide-IR 40 mg, in patients with chronic heart failure

    PubMed Central

    Ballester, Maria Rosa; Roig, Eulàlia; Gich, Ignasi; Puntes, Montse; Delgadillo, Joaquín; Santos, Benjamín; Antonijoan, Rosa Maria

    2015-01-01

    Purpose Diuretics are the primary treatment for the management of chronic heart failure (HF) symptoms and for the improvement of acute HF symptoms. The rate of delivery to the site of action has been suggested to affect diuretic pharmacodynamics. The main objective of this clinical trial was to explore whether a prolonged release tablet formulation of torasemide (torasemide-PR) was more natriuretically efficient in patients with chronic HF compared to immediate-release furosemide (furosemide-IR) after a single-dose administration. Moreover, the pharmacokinetics of torasemide-PR, furosemide-IR, and torasemide-IR were assessed in chronic HF patients as well as urine pharmacodynamics. Methods Randomized, open-label, blinded-endpoint, crossover, and single-dose Phase I clinical trial with three experimental periods. Torasemide-PR and furosemide-IR were administered as a single dose in a crossover fashion for the first two periods, and torasemide-IR 10 mg was administered for the third period. Blood and urine samples were collected at fixed timepoints. The primary endpoint was the natriuretic efficiency after administration of torasemide-PR and furosemide-IR, defined as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours. Results Ten patients were included and nine completed the study. Here, we present the results from nine patients. Torasemide-PR was more natriuretically efficient than furosemide-IR (0.096±0.03 mmol/μg vs 0.015±0.0007 mmol/μg; P<0.0001). Mictional urgency was lower and more delayed with torasemide-PR than with furosemide-IR. Conclusion In a study with a limited sample size, our results suggest that 10 mg of torasemide-PR is more natriuretically efficient than 40 mg of furosemide-IR after single-dose administration in patients with chronic HF over a 24-hour collection period. Further studies are necessary to evaluate potential pharmacodynamic differences between torasemide formulations and to

  11. Randomized, Open-Label Study of the Impact of Age on Booster Responses to the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Children in India

    PubMed Central

    Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

    2014-01-01

    In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have

  12. Prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depression: An open-label, multicenter, pilot study of efficacy, safety and effect on headache-related disability, depression, and anxiety

    PubMed Central

    Boudreau, Guy P; Grosberg, Brian M; McAllister, Peter J; Lipton, Richard B; Buse, Dawn C

    2015-01-01

    Background Chronic migraine is associated with significant headache-related disability and psychiatric comorbidity. OnabotulinumtoxinA (BOTOX®) is effective and well tolerated in the prophylactic treatment of chronic migraine. This study aimed to provide preliminary data on the efficacy and safety of prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depressive symptoms. Methods This was a prospective, open-label, multicenter pilot study. Eligible patients met International Classification of Headache Disorders 2nd edition Revision criteria for chronic migraine and had associated depressive symptoms, including Patient Health Questionnaire depression module scores of 5–19. Eligible participants received 155 units of onabotulinumtoxinA, according to the PREEMPT protocol, at baseline and week 12. Assessments included headache frequency, the Headache Impact Test™, the Migraine Disability Assessment, the Beck Depression Inventory®-II, the nine-item Patient Health Questionnaire depression module, and the seven-item Generalized Anxiety Disorder questionnaire. Adverse events were also monitored. Results Overall, 32 participants received treatment. At week 24, there were statistically significant mean (standard deviation [SD]) improvements relative to baseline in the number of headache/migraine-free days (+8.2 [5.8]) (P<0.0001) and in the number of headache/migraine days (−8.2 [5.8]) (P<0.0001) per 30-day period. In addition, there were significant improvements in Headache Impact Test scores (−6.3 [6.9]) (P=0.0001) and Migraine Disability Assessment scores (−44.2 [67.5]) (P=0.0058). From baseline to week 24, statistically significant improvements were also seen in Beck Depression Inventory-II (−7.9 [6.0]) (P<0.0001), Patient Health Questionnaire depression module (−4.3 [4.7]) (P<0.0001), and Generalized Anxiety Disorder questionnaire (−3.5 [5.0]) (P=0.0002) scores. No serious adverse events were reported. Adverse events

  13. Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study

    PubMed Central

    Horneff, Gerd; Burgos-Vargas, Ruben; Constantin, Tamas; Foeldvari, Ivan; Vojinovic, Jelena; Chasnyk, Vyacheslav G; Dehoorne, Joke; Panaviene, Violeta; Susic, Gordana; Stanevica, Valda; Kobusinska, Katarzyna; Zuber, Zbigniew; Mouy, Richard; Rumba-Rozenfelde, Ingrida; Breda, Luciana; Dolezalova, Pavla; Job-Deslandre, Chantal; Wulffraat, Nico; Alvarez, Daniel; Zang, Chuanbo; Wajdula, Joseph; Woodworth, Deborah; Vlahos, Bonnie; Martini, Alberto; Ruperto, Nicolino

    2014-01-01

    Objective To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). Methods CLIPPER is an ongoing, Phase 3b, open-label, multicentre study; the 12-week (Part 1) data are reported here. Subjects with eoJIA (2–17 years), ERA (12–17 years), or PsA (12–17 years) received ETN 0.8 mg/kg once weekly (maximum 50 mg). Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology (ACR) 30 criteria at week 12; secondary outcomes included JIA ACR 50/70/90 and inactive disease. Results 122/127 (96.1%) subjects completed the study (mean age 11.7 years). JIA ACR 30 (95% CI) was achieved by 88.6% (81.6% to 93.6%) of subjects overall; 89.7% (78.8% to 96.1%) with eoJIA, 83.3% (67.2% to 93.6%) with ERA and 93.1% (77.2% to 99.2%) with PsA. For eoJIA, ERA, or PsA categories, the ORs of ETN vs the historical placebo data were 26.2, 15.1 and 40.7, respectively. Overall JIA ACR 50, 70, 90 and inactive disease were achieved by 81.1, 61.5, 29.8 and 12.1%, respectively. Treatment-emergent adverse events (AEs), infections, and serious AEs, were reported in 45 (35.4%), 58 (45.7%), and 4 (3.1%), subjects, respectively. Serious AEs were one case each of abdominal pain, bronchopneumonia, gastroenteritis and pyelocystitis. One subject reported herpes zoster and another varicella. No differences in safety were observed across the JIA categories. Conclusions ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA, ERA and PsA, with no unexpected safety findings. PMID:23696632

  14. Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

    PubMed Central

    Choi, YoonJung; Lee, SeungHwan; Cho, Sang-Min; Kang, Won-Ho; Nam, Kyu-Yeol; Jang, In-Jin; Yu, Kyung-Sang

    2016-01-01

    Background A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94−1.01) and 0.97 (0.93−1.01), respectively. The corresponding values for losartan were 0.91 (0.81−1.02) and 1.05 (0.98−1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated. Conclusion An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0–t values. The amlodipine besylate

  15. Thai Adolescent Survivors 1 Year after the 2004 Tsunami: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Tuicomepee, Arunya; Romano, John L.

    2008-01-01

    This study examined the impact of the 2004 Asian tsunami on 400 Thai adolescents 1 year after the disaster. Quantitative analyses showed that youth behavior problems were positively associated with tsunami experiences and negatively associated with positive family functioning. Tsunami exposure, school connectedness, religious beliefs and…

  16. Ethosuximide for Essential Tremor: An Open-Label Trial

    PubMed Central

    Gironell, Alexandre; Marin-Lahoz, Juan

    2016-01-01

    Background T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Methods Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID). The main outcome measures were: 1) tremor clinical rating scale (TCRS) score, 2) accelerometric recordings, and 3) self-reported disability scale score. Results Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2), daily living activities (TCRS 3), or in the patients’ subjective assessment (TCRS 4) and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment. Discussion The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET. PMID:27625899

  17. BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase

    PubMed Central

    Larsen, Stig; Butthongkomvong, Kritiya; Manikhas, Alexey; Trishkina, Ekaterina; Poddubuskaya, Elena; Matrosova, Marina; Srimuninnimit, Vichien; Lindkær-Jensen, Steen

    2014-01-01

    The aims were to compare the efficacy and tolerability of a new benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) versus placebo and to investigate the long-term tolerability of BP-C1 in the treatment of patients with metastatic breast cancer. Material and methods A randomized, double-blind, placebo-controlled multicenter study was performed with a semi-crossover design. Patients allocated to placebo switched to BP-C1 after 32 days of treatment. Patients who completed 32 days of BP-C1 treatment were offered the opportunity to continue on BP-C1 for an additional 32 days in an open-label extension. Patients were then followed up for another 28 days. Thirty patients were given daily intramuscular injections of 0.035 mg/kg of body weight BP-C1 or placebo for 32 days. Biochemistry, hematology, National Cancer Institute Common Terminology Criteria for Adverse Events (CTC-NCI), European Organisation for Research and Treatment of Cancer quality of life questionnaire (QOL-C30 and the breast-cancer–specific BR23) data were recorded at screening and after every 16 days of treatment. Computed tomography was performed at screening and every 32 days. Results The sum of target lesions increased 2.4% in the BP-C1 group and 14.3% in the placebo group. Only the increase in the placebo group was significant (P=0.013). The difference between the groups was significant in favor of BP-C1 (P=0.04). There was a significant difference (P=0.026) in favor of BP-C1 regarding Response Evaluation Criteria In Solid Tumors (RECIST) classification. The sum of lesions increased slightly in the patients receiving 64 days of continuous BP-C1 treatment, of whom 68.4% were classified as responders. The sum CTC-NCI toxicity score increased nonsignificantly in the BP-C1 group but significantly in the placebo group (P=0.05). The difference in increase between groups did not meet the level of significance (P=0.12). The sum toxicity score was reduced in the patients

  18. Differing effects of PTH 1-34, PTH 1-84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT.

    PubMed

    Hansen, Stinus; Hauge, Ellen M; Beck Jensen, Jens-Erik; Brixen, Kim

    2013-04-01

    Whereas the beneficial effects of intermittent treatment with parathyroid hormone (PTH) (intact PTH 1-84 or fragment PTH 1-34, teriparatide) on vertebral strength is well documented, treatment may not be equally effective in the peripheral skeleton. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to detail effects on compartmental geometry, density, and microarchitecture as well as finite element (FE) estimated integral strength at the distal radius and tibia in postmenopausal osteoporotic women treated with PTH 1-34 (20 µg sc daily, n = 18) or PTH 1-84 (100 µg sc daily, n = 20) for 18 months in an open-label, nonrandomized study. A group of postmenopausal osteoporotic women receiving zoledronic acid (5 mg infusion once yearly, n = 33) was also included. Anabolic therapy increased cortical porosity in radius (PTH 1-34 32 ± 37%, PTH 1-84 39 ± 32%, both p < 0.001) and tibia (PTH 1-34 13 ± 27%, PTH 1-84 15 ± 22%, both p < 0.001) with corresponding declines in cortical density. With PTH 1-34, increases in cortical thickness in radius (2.0 ± 3.8%, p < 0.05) and tibia (3.8 ± 10.4%, p < 0.01) were found. Trabecular number increased in tibia with both PTH 1-34 (4.2 ± 7.1%, p < 0.05) and PTH 1-84 (5.3 ± 8.3%, p < 0.01). Zoledronic acid did not impact cortical porosity at either site but increased cortical thickness (3.0 ± 3.5%, p < 0.01), total (2.7 ± 2.5%, p < 0.001) and cortical density (1.5 ± 2.0%, p < 0.01) in tibia as well as trabecular volume fraction in radius (2.5 ± 5.1%, p < 0.05) and tibia (2.2 ± 2.2%, p < 0.01). FE estimated bone strength was preserved, but not increased, with PTH 1-34 and zoledronic acid at both sites, whereas it decreased with PTH 1-84 in radius (-2.8 ± 5.8%, p < 0.05) and tibia (-3.9 ± 4.8%, p < 0.001). Conclusively, divergent treatment-specific effects in cortical

  19. Early Neuropsychological Tests as Correlates of Productivity 1 Year after Traumatic Brain Injury: A Preliminary Matched Case-Control Study

    ERIC Educational Resources Information Center

    Ryu, Won Hyung A.; Cullen, Nora K.; Bayley, Mark T.

    2010-01-01

    This study explored the relative strength of five neuropsychological tests in correlating with productivity 1 year after traumatic brain injury (TBI). Six moderate-to-severe TBI patients who returned to work at 1-year post-injury were matched with six controls who were unemployed after 1 year based on age, severity of injury, and Functional…

  20. Effectiveness of hydrochlorothiazide in combination with telmisartan and olmesartan in adults with moderate hypertension not controlled with monotherapy: a prospective, randomized, open-label, blinded end point (PROBE), parallel-arm study

    PubMed Central

    Fogari, Roberto; Zoppi, Annalisa; Mugellini, Amedeo; Preti, Paola; Destro, Maurizio; Rinaldi, Andrea; Derosa, Giuseppe

    2008-01-01

    Background:The potential combinations of antihypertensive agents are many, and making rational choices depends on the characteristics of each drug and on their complementary mechanisms of action. Objective: The aim of this study was to evaluate the effectiveness of adding hydrochlorothiazide (HCTZ) 12.5 mg to olmesartan 20 mg or telmisartan 80 mg on blood pressure (BP) in patients with moderate hypertension. Methods: Consecutive outpatients at the Centro per l'Ipertensione e la Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy, of both sexes aged 39 to 75 years were considered eligible for enrollment if they had a sitting diastolic BP (DBP) ->99 mm Hg and <110 mm Hg at the end of an initial 2-week washout period. Patients were random- ized to olmesartan 20 mg QD or telmisartan 80 mg QD according to a prospective, open-label, blinded end point, parallel-arm design. After 8 weeks of monotherapy, patients whose BP was not controlled (DBP ->90 mm Hg) received HCTZ 12.5 mg QD for 8 additional weeks. Clinical and ambulatory BPs were measured at the end of the washout period and at the end of both treatment periods. Adverse events (AEs) were recorded from spontaneous reports and direct inquiry from investigators. Results: One hundred forty-five patients, all of whom were white, were recruited for the study. After the initial washout period, 13 patients did not meet the inclusion criteria and 6 refused to continue. A total of 126 white patients (69 men, 57 women; mean [SD] age, 60.2 [11.6] years) were randomized to receive monotherapy. Of these, 35 patients (56%) in the olmesartan group and 33 (52%) in the telmisartan group had previously received antihypertensive therapy. At the end of monotherapy, the 52 patients in the olmesartan group and the 49 patients in the telmisartan treatment group who were still in the study and had their BP inadequately controlled by treatment had HCTZ 12.5 mg QD added to their treatment regimen. Both combinations induced a

  1. Enteroaggregative Escherichia coli in Daycare—A 1-Year Dynamic Cohort Study

    PubMed Central

    Hebbelstrup Jensen, Betina; Stensvold, Christen R.; Struve, Carsten; Olsen, Katharina E. P.; Scheutz, Flemming; Boisen, Nadia; Röser, Dennis; Andreassen, Bente U.; Nielsen, Henrik V.; Schønning, Kristian; Petersen, Andreas M.; Krogfelt, Karen A.

    2016-01-01

    Enteroaggregative Escherichia coli (EAEC) has been associated with persistent diarrhea, reduced growth acceleration, and failure to thrive in children living in developing countries and with childhood diarrhea in general in industrialized countries. The clinical implications of an EAEC carrier-status in children in industrialized countries warrants clarification. To investigate the pathological significance of an EAEC carrier-state in the industrialized countries, we designed a 1-year dynamic cohort study and performed follow-up every second month, where the study participants submitted a stool sample and answered a questionnaire regarding gastrointestinal symptoms and exposures. Exposures included foreign travel, consumption of antibiotics, and contact with a diseased animal. In the capital area of Denmark, a total of 179 children aged 0–6 years were followed in a cohort study, in the period between 2009 and 2013. This is the first investigation of the incidence and pathological significance of EAEC in Danish children attending daycare facilities. Conventional microbiological detection of enteric pathogens was performed at Statens Serum Institute, Copenhagen, Denmark, and at Hvidovre Hospital, Copenhagen, Denmark. Parents completed questionnaires regarding gastrointestinal symptoms. The EAEC strains were further characterized by serotyping, phylogenetic analysis, and susceptibility testing. EAEC was detected in 25 (14%) of the children during the observational period of 1 year. One or more gastrointestinal symptoms were reported from 56% of the EAEC-positive children. Diarrhea was reported in six (24%) of the EAEC positive children, but no cases of weight loss, and general failure to thrive were observed. The EAEC strains detected comprised a large number of different serotypes, confirming the genetic heterogeneity of this pathotype. EAEC was highly prevalent (n = 25, 14%) in Danish children in daycare centers and was accompanied by gastrointestinal symptoms in

  2. Whooping cough in South-East Romania: a 1-year study.

    PubMed

    Dinu, Sorin; Guillot, Sophie; Dragomirescu, Cristiana Cerasella; Brun, Delphine; Lazăr, Stefan; Vancea, Geta; Ionescu, Biatrice Mariana; Gherman, Mariana Felicia; Bjerkestrand, Andreea-Florina-Dana; Ungureanu, Vasilica; Guiso, Nicole; Damian, Maria

    2014-03-01

    The incidence of whooping cough in Romania is substantially underestimated, and, as noted by the health authorities, this is mostly due to the lack of both awareness and biological diagnosis. We conducted a 1-year study in Bucharest in order to assess the circulation of Bordetella pertussis, the main etiological agent of whooping cough. Fifty-one subjects suspected of whooping cough were enrolled. Culture, real-time PCR, and enzyme-linked immunosorbent assay were used for laboratory diagnosis. Whooping cough patients (63%) were distributed among all age groups, and most were unvaccinated, incompletely vaccinated, or had been vaccinated more than 5 years previously. Bordetella holmesii DNA was detected in 22% of the bordetellosis cases; these patients included adults; teenagers; and, surprisingly, young children. B. pertussis isolates were similar to the clinical isolates currently circulating elsewhere in Europe. One isolate does not express pertactin, an antigen included in some acellular pertussis vaccines.

  3. Infant Aphakia Treatment Study: Effects of persistent fetal vasculature on outcome at 1 year of age

    PubMed Central

    Morrison, David G.; Wilson, M. Edward; Trivedi, Rupal H.; Lambert, Scott R.; Lynn, Michael J.

    2011-01-01

    Background The Infant Aphakia Treatment Study (IATS) is a randomized trial comparing the treatment of unilateral congenital cataract with primary intraocular lens (IOL) implantation versus aphakic contact lens (CL). The purpose of this study was to compare the outcomes for infants with lens opacity associated with persistent fetal vasculature (PFV) to those without. Methods Retrospective subgroup analysis of grating visual acuity at 1 year of age and adverse events up to 1 year after surgery in eyes identified intraoperatively as having evidence of mild PFV from the IATS. Results Of 83 infants, 18 (22%: 11 CL, 7 IOL) had PFV. Median logMAR visual acuity was 0.88 for patients with PFV and 0.80 for patients without PFV (P = 0.46). One or more adverse events up to one year after surgery occurred in 12 infants (67%) with PFV and 30 infants (46%) without PFV (P = 0.18). The incidence of adverse events was significantly higher in patients with PFV compared to patients without PFV in the CL group (55% vs 20%, P = 0.049) but not in the IOL group (86% vs 71%, P = 0.65), possibly because all children receiving IOLs had higher rates of adverse events when compared to aphakic children (73% vs 29%, P < 0.001). Conclusions Aphakic infants with mild PFV treated with CL had a higher incidence of adverse events following lensectomy compared to children with other forms of unilateral congenital cataract; nevertheless, similar visual outcomes at one year after surgery were obtained. PMID:22108353

  4. Study protocol for a phase III multicentre, randomised, open-label, blinded-end point trial to evaluate the efficacy and safety of immunoglobulin plus cyclosporin A in patients with severe Kawasaki disease (KAICA Trial)

    PubMed Central

    Aoyagi, Reiko; Hamada, Hiromichi; Sato, Yasunori; Suzuki, Hiroyuki; Onouchi, Yoshihiro; Ebata, Ryota; Terauchi, Moe; Terai, Masaru; Hanaoka, Hideki; Hata, Akira

    2015-01-01

    Introduction Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown aetiology that predominantly affects infants and young children. We hypothesise that cyclosporin A (CsA) may be effective in treating KD by regulating the Ca2+/NFAT signalling pathway. This trial compares the current standard therapy of intravenous immunoglobulin (IVIG) and the combined IVIG+CsA therapy in paediatric patients with severe KD. Methods and analysis This trial is a phase III, multicentre, randomised, open-label, blinded-end point trial that evaluates the efficacy and safety of IVIG+CsA therapy. Patients with severe KD who satisfy the eligibility criteria are randomised (1:1) to receive either CsA (5 mg/kg/day for 5 days; Neoral) plus high-dose IVIG (2 g/kg for 24 h and aspirin 30 mg/kg/day), or high-dose IVIG alone (2 g/kg for 24 h and aspirin 30 mg/kg/day). The primary end point is the frequency of occurrence of coronary artery abnormalities during the trial period. An independent end point review committee will be in charge of the trial assessment. Ethics and dissemination The protocol was approved by the Institutional Review Board of each institution. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, in Japan. The trial is currently on-going and is scheduled to finish in April 2017. The findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number JMA-IIA00174; Pre-results. PMID:26628527

  5. Six-Week Open-Label Reboxetine Treatment in Children and Adolescents with Attention-Deficit/hyperactivity Disorder.

    ERIC Educational Resources Information Center

    Ratner, Sharon; Laor, Nathaniel; Bronstein, Yifat; Weizman, Abraham; Toren, Paz

    2005-01-01

    Objective: This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) resistant to a previous methylphenidate trial. Method: Thirty-one child and adolescent outpatients, aged 8 to 18 (mean age, 11.7; SD = 2.87)…

  6. Efficacy and safety of tiotropium Respimat SMI in COPD in two 1-year randomized studies.

    PubMed

    Bateman, Eric; Singh, Dave; Smith, David; Disse, Bernd; Towse, Lesley; Massey, Dan; Blatchford, Jon; Pavia, Demetri; Hodder, Rick

    2010-08-09

    Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 microg versus placebo, inhaled via the Respimat Soft Mist Inhaler (SMI). The two studies were combined and had 4 co-primary endpoints (trough FEV(1) response, Mahler Transition Dyspnea Index [TDI] and St George's Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year). A total of 1990 patients with COPD participated (mean FEV(1): 1.09 L). The mean trough FEV(1) response of tiotropium 5 or 10 microg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001). The COPD exacerbation rate was significantly lower with tiotropium 5 microg (RR = 0.78; P = 0.002) and tiotropium 10 microg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001). Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment. Fatal events occurred in 2.4% (5 microg), 2.7% (10 microg), and 1.6% (placebo) of patients; these differences were not significant. Tiotropium Respimat SMI 5 microg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 microg dose but with a lower frequency of anticholinergic adverse events.

  7. Screening for refractive errors at age 1 year: a pilot study.

    PubMed Central

    Ingram, R M; Traynar, M J; Walker, C; Wilson, J M

    1979-01-01

    Cycloplegic refraction of 1-year-old children is technically possible and is acceptable to mothers as a method for screening children for visual defects. The range of refractions found in a sample of 186 1-year-old children is reported. Prediction of which children are significantly at risk for squint and/or amblyopia is possible on the basis of refractions at age 1 year according to the criteria selected for an 'abnormal' refraction. Bilateral hypermetropia and/or astigmatism or anisometropia at age 1 year was significantly (P less than 1 in 10 000) associated with a child eventually being found to have squint or amblyopia. Both the age of screening and criteria of abnormality will probably need modification. +2.50 or more D hypermetropia in any one meridian of either eye at age 1 year was even more significantly (P = 0.000 000 05%) associated with squint and/or amblyopia. The possibility that meridional hypermetropia could be the basic defect in squint and amblyopia is discussed. PMID:435441

  8. Raltegravir Non-Inferior to Nucleoside Based Regimens in SECOND-LINE Therapy with Lopinavir/Ritonavir over 96 Weeks: A Randomised Open Label Study for the Treatment Of HIV-1 Infection

    PubMed Central

    Amin, Janaki; Boyd, Mark A.; Kumarasamy, Nagalingeswaran; Moore, Cecilia L.; Losso, Marcello H.; Nwizu, Chidi A.; Mohapi, Lerato; Kerr, Stephen J.; Sohn, Annette H.; Teppler, Hedy; Renjifo, Boris; Molina, Jean-Michel; Emery, Sean; Cooper, David A.

    2015-01-01

    Objective To determine the durability over 96 weeks of safety and efficacy of lopinavir/ritonavir (LPV/r) and raltegravir (RAL) which was demonstrated to have non-inferior efficacy relative to a regimen of LPV/r with nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) (Control) in primary analysis at 48 weeks. Design Open label, centrally randomised trial. Setting Recruitment was from 37 primary and secondary care sites from Africa, Asia, Australia, Europe and Latin America. Subjects 541 HIV-1 infected adults virologically failing first-line non-NRTI + 2N(t)RTI, with no previous exposure to protease inhibitors or integrase strand transfer inhibitors were analysed, 425 completed 96 weeks follow up on randomised therapy. Intervention Randomisation was 1:1 to Control or RAL. Main outcome measures Differences between the proportion of participants with plasma HIV-1 RNA (VL) <200 copies/mL by intention to treat were compared with a non-inferiority margin of −12%. Differences in biochemical, haematological and metabolic changes were assessed using T-tests. Results VL <200 copies/mL at 96 weeks was: RAL 80.4%, Control 76.0% (difference: 4.4 [95%CI −2.6, 11.3]) and met non-inferiority criteria. The RAL arm had a significantly higher mean change (difference Control-RAL; 95%CI) in haemoglobin (−2.9; −5.7, −1.1), total lymphocytes (−0.2; −0.3, −0.0), total cholesterol (−0.5; −0.8, −0.3), HDL cholesterol (−0.1; −0.1, −0.0) and LDL cholesterol (−0.3; −0.5, −0.2). Conclusion At 96 weeks, both RAL and Control maintained efficacy greater than 75% and continued to demonstrate similar safety profiles. These results support the use of a combination LPV/r and RAL regimen as an option following failure of 1st line NNRTI + 2N(t)RTIs. Trial Registration ClinicalTrials.gov NCT00931463 PMID:25723472

  9. A 1-Year Study on the Detection of Human Enteric Viruses in New Caledonia.

    PubMed

    Kaas, Laetitia; Gourinat, Ann-Claire; Urbès, Florence; Langlet, Jérémie

    2016-03-01

    Human enteric viruses occur in high concentrations in wastewater and can contaminate receiving environmental waters. Due to the lack of data on the prevalence of enteric viruses in New Caledonia, the presence and the concentrations of enteric viruses in wastewater and seawater were determined. Untreated wastewater and seawater samples were collected monthly for 1 year from a wastewater treatment plant (WWTP) and from the WWTP's outlet, located directly on a popular recreational beach. Samples were tested for norovirus genogroups I and II (NoV GI and GII), astroviruses (AsV), sapoviruses (SaV), enteroviruses (EV), hepatitis A viruses (HAV), rotaviruses (RoV), human adenoviruses (HAdV) and human polyomaviruses (HPyV). To support these data, faecal samples from cases of gastroenteritis were tested for the first time for NoV and detected in the population. NoV GI, NoV GII, EV, SaV, HAdV and HPyV were detected in all wastewaters, RoV in 75% and AsV in 67%. HAV were not detected in wastewater. Overall, 92% of seawater samples were positive for at least one virus. HPyV were detected most frequently in 92% of samples and at concentrations up to 7.7 × 10(3) genome copies/L. NoV GI, NoV GII, EV, SaV, RoV and HAdV were found in 33, 66, 41, 33, 16 and 66% of seawater samples, respectively. AsV were not detected in seawater. This study reports for the first time the presence of NoV and other enteric viruses in New Caledonia and highlights the year-round presence of enteric viruses in the seawater of a popular beach.

  10. Effectiveness of a multidisciplinary heart failure disease management programme on 1-year mortality: Prospective cohort study.

    PubMed

    Laborde-Castérot, Hervé; Agrinier, Nelly; Zannad, Faiez; Mebazaa, Alexandre; Rossignol, Patrick; Girerd, Nicolas; Alla, François; Thilly, Nathalie

    2016-09-01

    We performed a multicenter prospective observational cohort study (Epidémiologie et Pronostic de l'Insuffisance Cardiaque Aiguë en Lorraine, Epidemiology and Prognosis of Acute Heart Failure in Lorraine [EPICAL2]) to evaluate the effectiveness on mortality of a community-based multidisciplinary disease management programme (DMP) for heart failure (HF) patients.Between October 2011 and October 2012, 1816 patients, who were hospitalized for acute HF or who developed acute HF during a hospitalization, were included from 21 hospitals in a northeast region of France. At hospital admission, their mean age was 77.3 (standard deviation [SD] 11.6) years and mean left ventricular ejection fraction was 45.0 (SD 16.0)%. A subset of patients were enrolled in a multidimensional DMP for HF (n = 312, 17.2%), based on structured patient education, home monitoring visits by HF-trained nurses, and automatic alerts triggered by significant clinical and biological changes to the patient. The DMP involved general practitioners, nurses, and cardiologists collaborating via an individual web-based medical electronic record. The outcome was all-cause mortality from the 3rd to the 12th month after discharge. During the follow-up, a total of 377 (20.8%) patients died: 321 (21.3%) in the control group and 56 (17.9%) in the DMP group. In a propensity score analysis, DMP was associated with lower 1-year all-cause mortality (hazard ratio 0.65, 95% CI 0.46-0.92). Instrumental variable analysis gave similar results (hazard ratio 0.56, 0.27-1.16).In a real world setting, a multidimensional DMP for HF with structured patient education, home nurse monitoring, and appropriate physician alerts may improve survival when implemented after discharge from hospitalization due to worsening HF.

  11. A 1-Year Study on the Detection of Human Enteric Viruses in New Caledonia.

    PubMed

    Kaas, Laetitia; Gourinat, Ann-Claire; Urbès, Florence; Langlet, Jérémie

    2016-03-01

    Human enteric viruses occur in high concentrations in wastewater and can contaminate receiving environmental waters. Due to the lack of data on the prevalence of enteric viruses in New Caledonia, the presence and the concentrations of enteric viruses in wastewater and seawater were determined. Untreated wastewater and seawater samples were collected monthly for 1 year from a wastewater treatment plant (WWTP) and from the WWTP's outlet, located directly on a popular recreational beach. Samples were tested for norovirus genogroups I and II (NoV GI and GII), astroviruses (AsV), sapoviruses (SaV), enteroviruses (EV), hepatitis A viruses (HAV), rotaviruses (RoV), human adenoviruses (HAdV) and human polyomaviruses (HPyV). To support these data, faecal samples from cases of gastroenteritis were tested for the first time for NoV and detected in the population. NoV GI, NoV GII, EV, SaV, HAdV and HPyV were detected in all wastewaters, RoV in 75% and AsV in 67%. HAV were not detected in wastewater. Overall, 92% of seawater samples were positive for at least one virus. HPyV were detected most frequently in 92% of samples and at concentrations up to 7.7 × 10(3) genome copies/L. NoV GI, NoV GII, EV, SaV, RoV and HAdV were found in 33, 66, 41, 33, 16 and 66% of seawater samples, respectively. AsV were not detected in seawater. This study reports for the first time the presence of NoV and other enteric viruses in New Caledonia and highlights the year-round presence of enteric viruses in the seawater of a popular beach. PMID:26670603

  12. Effectiveness of a multidisciplinary heart failure disease management programme on 1-year mortality: Prospective cohort study.

    PubMed

    Laborde-Castérot, Hervé; Agrinier, Nelly; Zannad, Faiez; Mebazaa, Alexandre; Rossignol, Patrick; Girerd, Nicolas; Alla, François; Thilly, Nathalie

    2016-09-01

    We performed a multicenter prospective observational cohort study (Epidémiologie et Pronostic de l'Insuffisance Cardiaque Aiguë en Lorraine, Epidemiology and Prognosis of Acute Heart Failure in Lorraine [EPICAL2]) to evaluate the effectiveness on mortality of a community-based multidisciplinary disease management programme (DMP) for heart failure (HF) patients.Between October 2011 and October 2012, 1816 patients, who were hospitalized for acute HF or who developed acute HF during a hospitalization, were included from 21 hospitals in a northeast region of France. At hospital admission, their mean age was 77.3 (standard deviation [SD] 11.6) years and mean left ventricular ejection fraction was 45.0 (SD 16.0)%. A subset of patients were enrolled in a multidimensional DMP for HF (n = 312, 17.2%), based on structured patient education, home monitoring visits by HF-trained nurses, and automatic alerts triggered by significant clinical and biological changes to the patient. The DMP involved general practitioners, nurses, and cardiologists collaborating via an individual web-based medical electronic record. The outcome was all-cause mortality from the 3rd to the 12th month after discharge. During the follow-up, a total of 377 (20.8%) patients died: 321 (21.3%) in the control group and 56 (17.9%) in the DMP group. In a propensity score analysis, DMP was associated with lower 1-year all-cause mortality (hazard ratio 0.65, 95% CI 0.46-0.92). Instrumental variable analysis gave similar results (hazard ratio 0.56, 0.27-1.16).In a real world setting, a multidimensional DMP for HF with structured patient education, home nurse monitoring, and appropriate physician alerts may improve survival when implemented after discharge from hospitalization due to worsening HF. PMID:27631204

  13. A prospective study of the 1-year incidence of fibromyalgia after acute whiplash injury

    PubMed Central

    Ferrari, Robert

    2015-01-01

    Objective To measure the 1-year incidence of fibromyalgia in a cohort of acute whiplash-injured participants. Methods Consecutive acute patients with whiplash were assessed via the 2010 Modified American College of Rheumatology (ACR) criteria for fibromyalgia at 3 months, 6 months and 1 year postinjury. At each of these follow-up points, participants were also examined for recovery from whiplash injury. Results Of an initial 268 participants, data on recovery was available for 264 participants during the 1-year follow-up period. At the 3-month follow-up, 62% (167/268) of participants reported recovery from their whiplash injuries. At 6 months, 76% (203/268) reported recovery, and at 1 year 82% (216/264) reported recovery. At 3 and 6 months follow-up none of the participants met the 2010 Modified ACR Criteria for fibromyalgia, but fibromyalgia criteria were met for 2 (of 264) seen at the 1-year follow-up, yielding a 1-year incidence of 0.8% (95% CI 0.1% to 3.0%). Conclusions In the primary care setting, a significant proportion of patients with whiplash recover from whiplash injury at 1 year, and the incidence of fibromyalgia after acute whiplash injury is very low. The impression that fibromyalgia is common after whiplash injury may be due to the failure to exclude precollision fibromyalgia cases or due to referral bias of non-recovered patients. PMID:26509044

  14. Phase III, Randomized, Open-Label Study of Daily Imatinib Mesylate 400 mg Versus 800 mg in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase Using Molecular End Points: Tyrosine Kinase Inhibitor Optimization and Selectivity Study

    PubMed Central

    Cortes, Jorge E.; Baccarani, Michele; Guilhot, François; Druker, Brian J.; Branford, Susan; Kim, Dong-Wook; Pane, Fabrizio; Pasquini, Ricardo; Goldberg, Stuart L.; Kalaycio, Matt; Moiraghi, Beatriz; Rowe, Jacob M.; Tothova, Elena; De Souza, Carmino; Rudoltz, Marc; Yu, Richard; Krahnke, Tillmann; Kantarjian, Hagop M.; Radich, Jerald P.; Hughes, Timothy P.

    2010-01-01

    Purpose To evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d (400 mg twice daily) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Patients and Methods A total of 476 patients were randomly assigned 2:1 to imatinib 800 mg (n = 319) or 400 mg (n = 157) daily. The primary end point was the major molecular response (MMR) rate at 12 months. Results At 12 months, differences in MMR and complete cytogenetic response (CCyR) rates were not statistically significant (MMR, 46% v 40%; P = .2035; CCyR, 70% v 66%; P = .3470). However, MMR occurred faster among patients randomly assigned to imatinib 800 mg/d, who had higher rates of MMR at 3 and 6 months compared with those in the imatinib 400-mg/d arm (P = .0035 by log-rank test). CCyR also occurred faster in the 800-mg/d arm (CCyR at 6 months, 57% v 45%; P = .0146). The most common adverse events were edema, gastrointestinal problems, and rash, and all were more common in patients in the 800-mg/d arm. Grades 3 to 4 hematologic toxicity also occurred more frequently in patients receiving imatinib 800 mg/d. Conclusion MMR rates at 1 year were similar with imatinib 800 mg/d and 400 mg/d, but MMR and CCyR occurred earlier in patients treated with 800 mg/d. Continued follow-up is needed to determine the clinical significance of earlier responses on high-dose imatinib. PMID:20008622

  15. An open-label, in-use study assessing the warming sensation accompanying IFF Flavour 316282 and the acceptability and local tolerability of a syrup containing paracetamol and pseudoephedrine for the short-term treatment of symptoms of an upper respiratory tract infection

    PubMed Central

    Monnet, Joëlle

    2015-01-01

    Objective: The primary objective was to assess the warming sensation caused by IFF Flavour 316282 in a syrup used for short-term treatment by patients suffering from nasal congestion and mild to moderate body pain, headache, fever or sore throat associated with an upper respiratory tract infection. Methods: A single cohort, single treatment arm, open-label study. Subjects received one 30 mL dose of syrup containing IFF Flavour 316282, paracetamol and pseudoephedrine and recorded onset and disappearance of any warming sensation in the mouth/throat. Subjects’ assessments of strength and appeal of the sensation, taste, texture and acceptability of the product was investigated using questionnaires. Results: A total of 56 subjects were included; 53 (94.6%) experienced a warming sensation. The median duration of the warming sensation was 114 s (95% confidence interval: 87–120 s). All subjects rated the syrup as excellent, good or fair for treating their symptoms; 100% and 94.6% of subjects respectively described texture and taste as excellent, good or fair. There were no safety concerns, and the syrup was well tolerated. Most subjects liked the warming sensation. Conclusions: IFF Flavour 316282 in a syrup for treatment of upper respiratory tract infection symptoms is associated with a warming sensation. The syrup is well tolerated, safe and palatable. PMID:26770771

  16. Does Sensitivity to Orthographic Regularities Influence Reading and Spelling Acquisition? A 1-Year Prospective Study

    ERIC Educational Resources Information Center

    Rothe, Josefine; Schulte-Körne, Gerd; Ise, Elena

    2014-01-01

    Recent studies focused on the influence of orthographic processing on reading and spelling performance. It was found that orthographic processing is an independent predictor of reading and spelling performance in different languages and children of different ages. This study investigated sensitivity to orthographic regularities in German-speaking…

  17. Prospective Prediction of Nonsuicidal Self-Injury: A 1-Year Longitudinal Study in Young Adults

    ERIC Educational Resources Information Center

    Glenn, Catherine R.; Klonsky, E. David

    2011-01-01

    Nonsuicidal self-injury (NSSI) has become a significant public health problem. Although numerous studies have examined cross-sectional psychological correlates of NSSI, there has been little research examining predictors of NSSI over time. The present study examined cross-sectional and longitudinal correlates of NSSI in 81 young adult…

  18. Targeted hypoglossal neurostimulation for obstructive sleep apnoea: a 1-year pilot study.

    PubMed

    Mwenge, Gimbada B; Rombaux, Philippe; Dury, Myriam; Lengelé, Benoît; Rodenstein, Daniel

    2013-02-01

    Continuous positive airway pressure (CPAP) is an effective but cumbersome treatment for obstructive sleep apnoea (OSA). Noncompliant patients need alternative therapies. We studied a tongue neurostimulation approach: targeted hypoglossal neurostimulation (THN) therapy with the aura6000™ System. A multi-contact electrode positioned around the main trunk of the twelfth nerve connected to an implanted pulse generator stimulates segments of the nerve, activating dilator muscles. The primary objective was to improve the polysomnographically determined apnoea/hypopnoea index (AHI) at 3 months, and maintain the improvement after 12 months of treatment. 13 out of 14 operated patients were successfully implanted. At 12 months, the AHI decreased from 45±18 to 21±17, a 53% reduction (p<0.001). The 4% oxygen desaturation index fell from 29±20 to 15±16 and the arousal index from 37±13 to 25±14, both p<0.001. The Epworth sleepiness scale decreased from 11±7 to 8±4 (p=0.09). THN was neither painful nor awakened patients, who all complied with therapy. There were two transient tongue paresis. The present study represents the longest study of any hypoglossal neurostimulation reported to date. We conclude that THN is safe and effective to treat OSA in patients not compliant with CPAP.

  19. A longitudinal, event-related potential pilot study of adult obsessive-compulsive disorder with 1-year follow-up

    PubMed Central

    Yamamuro, Kazuhiko; Okada, Koji; Kishimoto, Naoko; Ota, Toyosaku; Iida, Junzo; Kishimoto, Toshifumi

    2016-01-01

    Aim Earlier brain imaging research studies have suggested that brain abnormalities in obsessive-compulsive disorder (OCD) normalize as clinical symptoms improve. However, although many studies have investigated event-related potentials (ERPs) in patients with OCD compared with healthy control subjects, it is currently unknown whether ERP changes reflect pharmacological and psychotherapeutic effects. As such, the current study examined the neurocognitive components of OCD to elucidate the pathophysiological abnormalities involved in the disorder, including the frontal-subcortical circuits. Methods The Yale-Brown Obsessive-Compulsive Scale was used to evaluate 14 adult patients with OCD. The present study also included ten age-, sex-, and IQ-matched controls. The P300 and mismatch negativity (MMN) components during an auditory oddball task at baseline for both groups and after 1 year of treatment for patients with OCD were measured. Results Compared with controls, P300 amplitude was attenuated in the OCD group at Cz and C4 at baseline. Pharmacotherapy and psychotherapy treatment for 1 year reduced OCD symptomology. P300 amplitude after 1 year of treatment was significantly increased, indicating normalization compared with baseline at Fz, Cz, C3, and C4. We found no differences in P300 latency, MMN amplitude, or MMN latency between baseline and after one year of treatment. Conclusion ERPs may be a useful tool for evaluating pharmacological and cognitive behavioral therapy in adult patients with OCD. PMID:27713631

  20. Sutureless femtosecond anterior lamellar keratoplasty: A 1-year follow-up study

    PubMed Central

    Shetty, Rohit; Nagaraja, Harsha; Veluri, Himabindu; Shivanna, Yathish; Kugar, Thungappa; Nujits, Rudy; Shetty, Bhujang

    2014-01-01

    Aim: To study the safety and efficacy of sutureless femtosecond anterior lamellar keratoplasty (FALK) in patients with corneal stromal opacities. Materials and Methods: Eleven eyes of 11 consecutive patients with corneal stromal opacities involving < 250 μ due to various pathologies were included in the study. Preoperatively, all underwent anterior segment imaging with spectral domain optical coherence tomography (SD-OCT) (Bioptigen Inc., Durham, North Carolina, USA) to measure the depth of the stromal opacity. All patients underwent FALK, and bandage contact lens was placed for a period of 2 weeks. Postoperatively, uncorrected visual acuity, best corrected visual acuity (BCVA), and SD-OCT evaluation were performed. Results: All patients showed significant improvement in BCVA. The mean postoperative BCVA (in decimals) improved from 0.11 ± 0.06 preoperatively to 0.59 ± 0.08. There were no intraoperative or significant postoperative complications that were noticed. Conclusion: FALK is a safe and effective alternative to deep anterior lamellar keratoplasty or penetrating keratoplasty in the treatment of anterior stromal opacities. PMID:25370393

  1. Video game addiction and college performance among males: results from a 1 year longitudinal study.

    PubMed

    Schmitt, Zachary L; Livingston, Michael G

    2015-01-01

    This study explored the pattern of video game usage and video game addiction among male college students and examined how video game addiction was related to expectations of college engagement, college grade point average (GPA), and on-campus drug and alcohol violations. Participants were 477 male, first year students at a liberal arts college. In the week before the start of classes, participants were given two surveys: one of expected college engagement, and the second of video game usage, including a measure of video game addiction. Results suggested that video game addiction is (a) negatively correlated with expected college engagement, (b) negatively correlated with college GPA, even when controlling for high school GPA, and (c) negatively correlated with drug and alcohol violations that occurred during the first year in college. Results are discussed in terms of implications for male students' engagement and success in college, and in terms of the construct validity of video game addiction. PMID:25584728

  2. Video game addiction and college performance among males: results from a 1 year longitudinal study.

    PubMed

    Schmitt, Zachary L; Livingston, Michael G

    2015-01-01

    This study explored the pattern of video game usage and video game addiction among male college students and examined how video game addiction was related to expectations of college engagement, college grade point average (GPA), and on-campus drug and alcohol violations. Participants were 477 male, first year students at a liberal arts college. In the week before the start of classes, participants were given two surveys: one of expected college engagement, and the second of video game usage, including a measure of video game addiction. Results suggested that video game addiction is (a) negatively correlated with expected college engagement, (b) negatively correlated with college GPA, even when controlling for high school GPA, and (c) negatively correlated with drug and alcohol violations that occurred during the first year in college. Results are discussed in terms of implications for male students' engagement and success in college, and in terms of the construct validity of video game addiction.

  3. Pro-/Antiinflammatory Dysregulation in Early Psychosis: Results from a 1-Year Follow-Up Study

    PubMed Central

    García-Bueno, Borja; Bioque, Miquel; MacDowell, Karina S.; Santabárbara, Javier; Martínez-Cengotitabengoa, Mónica; Moreno, Carmen; Sáiz, Pilar A.; Berrocoso, Esther; Gassó, Patricia; Fe Barcones, M.; González-Pinto, Ana; Parellada, Mara; Bobes, Julio; Micó, Juan A.; Bernardo, Miguel

    2015-01-01

    Background: Previous studies indicated a systemic deregulation of the pro-/antiinflammatory balance in subjects after 6 months of a first psychotic episode. This disruption was reexamined 12 months after diagnosis to identify potential risk/protective factors and associations with symptom severity. Methods: Eighty-five subjects were followed during 12 months and the determination of the same pro-/antiinflammatory mediators was carried out in plasma and peripheral blood mononuclear cells. Multivariate logistic regression analyses were used to identify risk/protective factors. Multiple linear regression models were performed to detect the change of each biological marker during follow-up in relation to clinical characteristics and confounding factors. Results: This study suggests a more severe systemic pro-/antiinflammatory deregulation than in earlier pathological stages in first psychotic episode, because not only were intracellular components of the inflammatory response increased but also the majority of soluble elements. Nitrite plasma levels and cyclooxygenase-2 expression in peripheral blood mononuclear cells are reliable potential risk factors and 15d-prostaglandin-J2 plasma levels a protection biomarker. An interesting relationship exists between antipsychotic dose and the levels of prostaglandin-E2 (inverse) and 15d-prostaglandin-J2 (direct). An inverse relationship between the Global Assessment of Functioning scale and lipid peroxidation is also present. Conclusions: Summing up, pro-/antiinflammatory mediators can be used as risk/protection biomarkers. The inverse association between oxidative/nitrosative damage and the Global Assessment of Functioning scale, and the possibility that one of the targets of antipsychotics could be the restoration of the pro-/antiinflammatory balance support the use of antiinflammatory drugs as coadjuvant to antipsychotics. PMID:25577666

  4. Diffusion tensor imaging study of pediatric patients with congenital hydrocephalus: 1-year postsurgical outcomes.

    PubMed

    Mangano, Francesco T; Altaye, Mekibib; McKinstry, Robert C; Shimony, Joshua S; Powell, Stephanie K; Phillips, Jannel M; Barnard, Holly; Limbrick, David D; Holland, Scott K; Jones, Blaise V; Dodd, Jonathan; Simpson, Sarah; Mercer, Deanna; Rajagopal, Akila; Bidwell, Sarah; Yuan, Weihong

    2016-09-01

    OBJECTIVE The purpose of this study was to investigate white matter (WM) structural abnormalities using diffusion tensor imaging (DTI) in children with hydrocephalus before CSF diversionary surgery (including ventriculoperitoneal shunt insertion and endoscopic third ventriculostomy) and during the course of recovery after surgery in association with neuropsychological and behavioral outcome. METHODS This prospective study included 54 pediatric patients with congenital hydrocephalus (21 female, 33 male; age range 0.03-194.5 months) who underwent surgery and 64 normal controls (30 female, 34 male; age range 0.30-197.75 months). DTI and neurodevelopmental outcome data were collected once in the control group and 3 times (preoperatively and at 3 and 12 months postoperatively) in the patients with hydrocephalus. DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were extracted from the genu of the corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). Group analysis was performed first cross-sectionally to quantify DTI abnormalities at 3 time points by comparing the data obtained in the hydrocephalus group for each of the 3 time points to data obtained in the controls. Longitudinal comparisons were conducted pairwise between different time points in patients whose data were acquired at multiple time points. Neurodevelopmental data were collected and analyzed using the Adaptive Behavior Assessment System, Second Edition, and the Bayley Scales of Infant Development, Third Edition. Correlation analyses were performed between DTI and behavioral measures. RESULTS Significant DTI abnormalities were found in the hydrocephalus patients in both the gCC (lower FA and higher MD, AD, and RD) and the PLIC (higher FA, lower AD and RD) before surgery. The DTI measures in the gCC remained mostly abnormal at 3 and 12 months after surgery. The DTI abnormalities in the PLIC were

  5. Salivary Anionic Changes after Radiotherapy for Nasopharyngeal Carcinoma: A 1-Year Prospective Study

    PubMed Central

    Pow, Edmond H. N.; Chen, Zhuofan; Kwong, Dora L. W.; Lam, Otto L. T.

    2016-01-01

    Objectives To investigate the salivary anionic changes of patients with nasopharyngeal carcinoma (NPC) treated by radiotherapy. Material and Methods Thirty-eight patients with T1-4, N0-2, M0 NPC received conventional radiotherapy. Stimulated whole saliva was collected at baseline and 2, 6 and 12 months after radiotherapy. Salivary anions levels were measured using ion chromatography. Results A reduction in stimulated saliva flow and salivary pH was accompanied by sustained changes in anionic composition. At 2 months following radiotherapy, there was a significant increase in chloride, sulphate, lactate and formate levels while significant reductions in nitrate and thiocyanate levels were found. No further changes in these anion levels were observed at 6 and 12 months. No significant changes were found in phosphate, acetate, or propionate levels throughout the study period. Conclusions Conventional radiotherapy has a significant and prolonged impact on certain anionic species, likely contributing to increased cariogenic properties and reduced antimicrobial capacities of saliva in NPC patients post-radiotherapy. PMID:27031997

  6. DTI study of Children with Congenital Hydrocephalus: 1 Year Post-Surgical Outcomes

    PubMed Central

    Mangano, Francesco T.; Altaye, Mekibib; McKinstry, Robert C.; Shimony, Joshua S.; Powell, Stephanie K.; Phillips, Jannel M.; Barnard, Holly; Limbrick, David D.; Holland, Scott K.; Jones, Blaise V.; Dodd, Jonathon; Simpson, Sarah; Deanna, Mercer; Rajagopal, Akila; Bidwell, Sarah; Yuan, Weihong

    2016-01-01

    Object To investigate white matter structural abnormalities using diffusion tensor imaging (DTI) in children with hydrocephalus before CSF diversionary surgery (including ventriculoperitoneal shunting and endoscopic third ventriculoscopy) and the course of recovery post-surgery in association with neuropsychological and behavioral outcome. Methods This was a prospective study that included 54 children with congenital hydrocephalus (21F/33M; age range: 0.03–194.5 months) who underwent surgery and 64 normal controls (30F/34M, age range: 0.30–197.75 months). DTI and neurodevelopmental outcome data were collected once in the control group and at pre-surgery, 3-month, and 12-month post-surgery in the patients. DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were extracted from the genu of corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). Group analysis was performed first cross-sectionally to quantify DTI abnormalities at three time points by comparing the controls and the patients group at the three time points separately. Longitudinal comparisons were conducted pairwise between different time points in patients whose data were acquired at multiple time points. Neurodevelopmental data were collected and analyzed using the Adaptive Behavior Assessment System, Second Edition (ABAS-II) and the Bayley Scales of Infant Development, Third Edition (Bayley-III). Correlation analyses were performed between DTI and behavioral outcomes. Results Significant DTI abnormalities were found in both the gCC (lower FA and higher MD, AD, and RD) and the PLIC (higher FA, lower AD and RD) at pre-surgery. The DTI measures in the gCC remained mostly abnormal at 3-month and 12-month post-surgery. The DTI abnormalities in the PLIC were significant in FA and AD at 3-month post-surgery but did nor persist when tested at 12-month post-surgery. Significant longitudinal DTI changes in the

  7. Patient satisfaction with mini-implant stabilised full dentures. A 1-year prospective study.

    PubMed

    Tomasi, C; Idmyr, B-O; Wennström, J L

    2013-07-01

    The purpose of this study was to evaluate patient-centred outcomes with regard to function and comfort after placement of mini-implants for stabilisation of complete dentures. The trial was designed as a prospective cohort of 12-months duration and involved 21 subjects in the age of 50-90 years having a full denture in the maxilla or the mandible with poor stability during function. Flapless installation of 2-4 narrow-body Dentatus Atlas(®) implants was performed and retention for the existing denture was obtained by the use of a silicone-based soft lining material (Tuf-Link(®)). Patients' judgement of perceived satisfaction with function and comfort of the dentures was recorded at baseline, 1- and 12-months post-treatment using 10-centimetre visual analogue scales (VAS) and a questionnaire. Clinical examination of the conditions of the peri-implant soft tissues was performed at 12 months. Nineteen of the 21 patients were available for the 12-month follow-up examination. The two drop-out subjects lost all implants within 1 month and rejected retreatment. Further six subjects lost 1-2 implants, but were sucessfully retreated by insertion of new implants. Overall satisfaction, chewing and speaking comfort were all markedly improved from pre-treatment median VAS scores of around 4-5 to median scores of 9·0-10 (10 = optimal) at the final examination. The prevalence of positive answers to questions regarding stability/function of the denture increased significantly to almost 100% for all questions. Treatment involving maxillary dentures and the use of short implants (7-10 mm) was associated with an increased risk of implant failure. The results indicate that placement of mini-implants as retentive elements for full dentures with poor functional stability has a marked positive impact on the patients' perception of oral function and comfort as well as security in social life.

  8. Emergency contraception with a Copper IUD or oral levonorgestrel: an observational study of 1-year pregnancy rates

    PubMed Central

    Turok, David K.; Jacobson, Janet C.; Dermish, Amna I.; Simonsen, Sara E.; Gurtcheff, Shawn; McFadden, Molly; Murphy, Patricia A.

    2014-01-01

    Objective We investigated the one-year pregnancy rates for emergency contraception (EC) users who selected the copper T380 IUD or oral levonorgestrel (LNG) for EC. Study Design This prospective study followed women for 1 year after choosing either the copper T380 IUD or oral LNG for EC. The study was powered to detect a 6% difference in pregnancy rates within the year after presenting for EC. Results Of the 542 women who presented for EC, agreed to participate in the trial, and meet inclusion criteria, 215 (40%) chose the copper IUD and 327 (60%) chose oral LNG. In the IUD group, 127 (59%) were nulligravid. IUD insertion failed in 42 women (19%). The 1-year follow-up rate was 443/542 (82%); 64% of IUD users contacted at 1 year still had their IUDs in place. The 1-year cumulative pregnancy rate in women choosing the IUD was 6.5% vs. 12.2% in those choosing oral LNG (HR= 0.53, 95% CI: 0.29–0.97, p=0.041). By type of EC method actually received, corresponding values were 5.2% for copper IUD users vs. 12.3% for oral LNG users, HR 0.42 (95% CI: 0.20–0.85, p= 0.017). A multivariable logistic regression model controlling for demographic variables demonstrates that women who chose the IUD for EC had fewer pregnancies in the following year than those who chose oral LNG (HR 0.50, 95% CI: 0.26–0.96, p=0.037). Conclusion One year after presenting for EC women choosing the copper IUD for EC were half as likely to have a pregnancy compared to those choosing oral LNG. PMID:24332433

  9. An open-label, single-center, phase IV clinical study of the effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) in reducing the duration and symptoms of the common cold in school-aged subjects.

    PubMed

    McElroy, Betty Howell; Miller, Shelley Porter

    2003-01-01

    Each year, more than 62 million cases of the common cold in the United States require medical attention and more than 80% affect school-aged children. The objective of this prospective, intent-to-treat, phase IV study was to determine the therapeutic and prophylactic effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) for the common cold. Zinc lozenges were administered once daily during the cold season for prophylaxis. For therapeutic purposes, lozenges were given 4 times per day. The primary objective of the study was the treatment effect on cold duration, and the secondary objective was the effect on the number of common colds. A putative control from our previous study was used for comparison. A total of 178 children, ages 12 to 18 years, was enrolled, of which 134 met criteria for efficacy analysis. The average cold duration with therapeutic lozenge use was 6.9 +/- 3.1 days, significantly shorter than the 9.0 +/- 3.5 days found in the control group (P < 0.001). The mean number of colds was 1.28 +/- 1.03 with zinc lozenge prophylaxis versus 1.7 +/- 1.91 without prophylaxis (P < 0.05), a 25% reduction. With prophylaxis, 25% of the subjects did not experience a cold and two-thirds never had a cold or only had 1 cold. There was no antibiotic use for any cold, and there were no adverse events reported. Results of this study are consistent with those from our previous retrospective study showing significantly shorter cold duration and fewer colds with the use of zinc gluconate glycine lozenges. The zinc gluconate glycine lozenges are well tolerated and are an easy-to-administer therapy that has the potential to substantially reduce cold-related school absences and antibiotic use and misuse as well as to provide a cost saving. PMID:12975716

  10. Effect of methylphenidate on the quality of life in children with epilepsy and attention deficit hyperactivity disorder: and open-label study using an osmotic-controlled release oral delivery system.

    PubMed

    Yoo, Hanik K; Park, Subin; Wang, Hee-Ryung; Lee, Joong Sun; Kim, Kunwoo; Paik, Kyoung-Won; Yum, Mi Sun; Ko, Tae-Sung

    2009-12-01

    This open study explored whether methylphenidate could be tolerated and effective in improving the quality of life (QOL) and attention deficit hyperactivity disorder (ADHD) symptoms of children with epilepsy and ADHD. Twenty-five subjects (aged 10.1 +/- 3.0 years) with ADHD and epilepsy were recruited at an outpatient clinic in Seoul, Korea. We used the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), ADHD rating scale (ARS) and clinical global impression (CGI) in this study. Osmotic-controlled release oral delivery system (OROS) methylphenidate, 1.0 +/- 0.4 mg/kg/day, was administered for 55.2 +/- 7.5 days. The QOL subscales including physical restriction (p = 0.005), self-esteem (p = 0.002), memory (p < 0.001), language (p = 0.005), other cognition (p < 0.001), social interaction (p = 0.002), behaviour (p < 0.001), general health (p = 0.002) and QOL (p < 0.001) were significantly increased and the ARS (p < 0.001) and CGI-Severity of illness scores (p < 0.001) were significantly reduced after medication. Although 60% of subjects had experienced adverse effects, most were tolerable and only two subjects withdrew from the study owing to unbearable adverse effects (anorexia and insomnia). Two subjects had seizure attacks during the study period without having to discontinue the trial drug. Despite limitations related to the small sample size and the open design of the present pilot study, our results suggest that OROS methylphenidate may be well tolerated and effective in reducing ADHD symptoms and improving QOL in this patient population. PMID:20007067

  11. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

    PubMed

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-03-01

    The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children <2 years of age (mean age: 15.8 months). During the 4-day follow-up period, pain (31.7%) and redness (27.3%) were the most frequent solicited local symptoms. Pain (2%) was also the most frequent grade 3 local symptom. One subject reported 2 serious adverse events that were not causally related to the study vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years.

  12. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study

    PubMed Central

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-01-01

    abstract The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children <2 years of age (mean age: 15.8 months). During the 4-day follow-up period, pain (31.7%) and redness (27.3%) were the most frequent solicited local symptoms. Pain (2%) was also the most frequent grade 3 local symptom. One subject reported 2 serious adverse events that were not causally related to the study vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years. PMID:26337197

  13. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects with Diagnosed Atopic Dermatitis

    PubMed Central

    Greenberg, Richard N; Hurley, Yadira; Dinh, Dinh V.; Mraz, Serena; Vera, Javier Gomez; von Bredow, Dorothea; von Krempelhuber, Alfred; Roesch, Siegfried; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Meyer, Thomas Peter; Schmidt, Darja; Nichols, Richard; Young, Philip; Chaplin, Paul

    2015-01-01

    Background Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers. Objective This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects. Methods Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored. Results The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects. Limitations The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%. Conclusion MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD. Trial Registration ClinicalTrials.gov NCT00316602 PMID:26439129

  14. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial.

    PubMed

    Al-Ali, Haifa Kathrin; Griesshammer, Martin; le Coutre, Philipp; Waller, Cornelius F; Liberati, Anna Marina; Schafhausen, Philippe; Tavares, Renato; Giraldo, Pilar; Foltz, Lynda; Raanani, Pia; Gupta, Vikas; Tannir, Bayane; Ronco, Julian Perez; Ghosh, Jagannath; Martino, Bruno; Vannucchi, Alessandro M

    2016-09-01

    JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis - a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib's mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov. PMID:27247324

  15. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial

    PubMed Central

    Al-Ali, Haifa Kathrin; Griesshammer, Martin; le Coutre, Philipp; Waller, Cornelius F.; Liberati, Anna Marina; Schafhausen, Philippe; Tavares, Renato; Giraldo, Pilar; Foltz, Lynda; Raanani, Pia; Gupta, Vikas; Tannir, Bayane; Ronco, Julian Perez; Ghosh, Jagannath; Martino, Bruno; Vannucchi, Alessandro M.

    2016-01-01

    JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis – a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib’s mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov. PMID:27247324

  16. Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma.

    PubMed

    Brander, Danielle; Rizzieri, David; Gockerman, Jon; Diehl, Louis; Shea, Thomas Charles; Decastro, Carlos; Moore, Joseph O; Beaven, Anne

    2013-12-01

    PTK787/ZK222584 (vatalanib), an orally active inhibitor of vascular endothelial growth factor receptors (VEGFRs), was evaluated in this phase II study of 20 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received once-daily PTK787/ZK222584 at a target dose of 1250 mg. Eighteen patients were evaluable for response: one patient had a complete response (CR), six patients had stable disease but subsequently progressed, 10 patients had progressive disease by three cycles and one subject withdrew before response evaluation. The patient who attained a CR underwent autologous stem cell transplant and remains disease-free 76 months after study completion. There were no grade 4 toxicities. Grade 3 thrombocytopenia occurred in 20% and grade 3 hypertension occurred in 10%. There were no episodes of grade 3 proteinuria. In conclusion, PTK787/ZK222584 was well tolerated in a heavily pretreated population of patients with DLBCL, although its therapeutic potential as a single agent in DLBCL appears limited. PMID:23488610

  17. ARE OPEN-LABEL PLACEBOS ETHICAL? INFORMED CONSENT AND ETHICAL EQUIVOCATIONS

    PubMed Central

    Blease, Charlotte; Colloca, Luana; Kaptchuk, Ted J

    2016-01-01

    The doctor-patient relationship is built on an implicit covenant of trust yet it was not until the post-World War Two era that respect for patient autonomy emerged as an article of mainstream medical ethics. Unlike their medical forebearers physicians today are expected to furnish patients with adequate information about diagnoses, prognoses and treatments. Against these dicta there has been ongoing debate over whether placebos pose a threat to patient autonomy. A key premise underlying medical ethics discussion is the notion that the placebo effect necessitates patient deception. Indeed, the American Medical Association guidelines imply that placebo treatment necessary entails a form of deception. As a consequence of this assumption, the fulcrum of debate on the use of placebo treatment has hinged on whether that deception is ever justified.. Recently performed experiments with open-label transparently prescribed placebos have begun to challenge the notion that deception is necessary in eliciting the placebo effect AND SUCH EFFECTS NECESSARILY INVOLVE A BINARY DISTIINCTION BETWEEN AUTONOMY AND BENEFICIENCE. In this paper we focus on the content of disclosures in distinctive open-label, transparently disclosed placebo studies and inquire whether they might be said to invoke deception in clinical contexts, and if so, whether the deception is unethical. We find that open placebos may be said to involve equivocation over how placebos work. However, drawing on surveys of patient attitudes we suggest that this equivocation appears to be acceptable to patients. We conclude that open placebos fulfil current American Medical Association guidelines for placebo use, and propose future research directions for harnessing the placebo effect ethically. PMID:26840547

  18. Efficacy and safety of a herbal mixture (Viron® tablets) in the treatment of patients with chronic hepatitis C virus infection: a prospective, randomized, open-label, proof-of-concept study

    PubMed Central

    Shawkat, Hisham; Yakoot, Mostafa; Shawkat, Tarek; Helmy, Sherine

    2015-01-01

    Background Development of an optimal interferon-free regimen for chronic hepatitis C virus infection is believed to require the combination of different drug classes to provide good antiviral efficacy, clinical and quality of life benefits, as well as a high barrier to resistance. Viron® is a new herbal drug in film-coated tablet form, and is based on a mixture of herbs with known hepatoprotective and antiviral properties. We conducted this study to explore the safety and the potential clinical and quality of life benefits of this product in patients with chronic hepatitis C infection. Methods Eighty-two consecutive patients presenting to our outpatient clinics as already-known or newly-diagnosed cases of chronic hepatitis C virus (HCV) infection, were entered into the study and randomized to three groups to receive escalating doses of Viron for 6 months. Virological, clinical, and enzyme responses, as well as quality of life index scores for chronic liver disease were compared between the groups. Results Of the 20 patients treated with the highest dose of Viron (three tablets twice daily), two (10%) had a complete virological response at the end of treatment (ETR) and two (10%) had a partial ETR, defined as a decrease in viral load of at least 2-log10 at the end of 6 months of treatment, whereas patients treated with the medium dose (two tablets twice daily) and the lowest dose (one tablet twice daily) showed a significantly lower ETR (P=0.043). Alanine aminotransferase levels and scores on the Chronic Liver Disease Questionnaire improved to a significantly greater extent in the highest dose group (P=0.007 and P=0.021, respectively). No serious adverse effects attributable to the herbal formulation were reported in any of the groups, apart from mild transient nausea, bloating, giddiness, and headache in two patients in the group receiving two tablets twice daily and in three patients in the group receiving three tablets twice daily. Conclusion We conclude that

  19. Identifying high-school dance students who will develop an eating disorder: a 1-year prospective study.

    PubMed

    Tseng, Mei-Chih Meg; Fang, David; Chang, Chin-Hao; Lee, Ming-Been

    2013-10-30

    This study examined the changes in eating disorder (ED) status over 1 year and identified risk factors for EDs among female dance students. In 2003, all students enrolled in each of the nation's 12 high schools with gifted dance programs participated in a two-phase survey. The same participants were invited to take part in a follow-up survey 1 year later. In all, 583 persons completed the phase 1 questionnaire survey, and 245 persons completed interviews twice at baseline and follow-up. Thirty-five females had a newly developed ED, and less than half of the ED cases found at baseline had recovered at follow-up. Being a grade 12 student carried a reduced risk of EDs, whereas higher baseline scores on the Bulimic Investigatory Test Edinburgh (BITE) increased risks of developing an ED after 1 year. A 10-item BITE questionnaire validly identified girl dance students who would develop EDs later in high school. EDs were more commonly developed during middle adolescence, and we suggest that prevention work against EDs begin in this period among the dance student population. The brief screening questionnaire might help detect intervention targets of a prevention program among adolescent dance students.

  20. An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for treating erectile dysfunction in men naïve to treatment.

    PubMed

    Safarinejad, M R; Shafiei, N; Safarinejad, S

    2010-01-01

    Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED.

  1. An open-label study examining the effect of pharmacological treatment on mannitol- and exercise-induced airway hyperresponsiveness in asthmatic children and adolescents with exercise-induced bronchoconstriction

    PubMed Central

    2014-01-01

    Background Mannitol- and exercise bronchial provocation tests are both used to diagnose exercise-induced bronchoconstriction. The study aim was to compare the short-term treatment response to budesonide and montelukast on airway hyperresponsiveness to mannitol challenge test and to exercise challenge test in children and adolescents with exercise-induced bronchoconstriction. Methods Patients were recruited from a paediatric asthma rehabilitation clinic located in the Swiss Alps. Individuals with exercise-induced bronchoconstriction and a positive result in the exercise challenge test underwent mannitol challenge test on day 0. All subjects then received a treatment with 400 μg budesonide and bronchodilators as needed for 7 days, after which exercise- and mannitol-challenge tests were repeated (day 7). Montelukast was then added to the previous treatment and both tests were repeated again after 7 days (day 14). Results Of 26 children and adolescents with exercise-induced bronchoconstriction, 14 had a positive exercise challenge test at baseline and were included in the intervention study. Seven of 14 (50%) also had a positive mannitol challenge test. There was a strong correlation between airway responsiveness to exercise and to mannitol at baseline (r = 0.560, p = 0.037). Treatment with budesonide and montelukast decreased airway hyperresponsiveness to exercise challenge test and to a lesser degree to mannitol challenge test. The fall in forced expiratory volume in one second during exercise challenge test was 21.7% on day 0 compared to 6.7% on day 14 (p = 0.001) and the mannitol challenge test dose response ratio was 0.036%/mg on day 0 compared to 0.013%/mg on day 14 (p = 0.067). Conclusion Short-term treatment with an inhaled corticosteroid and an additional leukotriene receptor antagonist in children and adolescents with exercise-induced bronchoconstriction decreases airway hyperresponsiveness to exercise and to mannitol. PMID:25084607

  2. An innovative intervention for the treatment of cognitive impairment–Emisymmetric bilateral stimulation improves cognitive functions in Alzheimer’s disease and mild cognitive impairment: an open-label study

    PubMed Central

    Guerriero, Fabio; Botarelli, Emanuele; Mele, Gianni; Polo, Lorenzo; Zoncu, Daniele; Renati, Paolo; Sgarlata, Carmelo; Rollone, Marco; Ricevuti, Giovanni; Maurizi, Niccolo; Francis, Matthew; Rondanelli, Mariangela; Perna, Simone; Guido, Davide; Mannu, Piero

    2015-01-01

    Background and aims In the last decade, the development of different methods of brain stimulation by electromagnetic fields (EMF) provides a promising therapeutic tool for subjects with impaired cognitive functions. Emisymmetric bilateral stimulation (EBS) is a novel and innovative EMF brain stimulation, whose working principle is to introduce very weak noise-like stimuli through EMF to trigger self-arrangements in the cortex of treated subjects, thereby improving cognitive faculties. The aim of this pilot study was to investigate in patients with cognitive impairment the effectiveness of EBS treatment with respect to global cognitive function, episodic memory, and executive functions. Methods Fourteen patients with cognitive decline (six with mild cognitive impairment and eight with Alzheimer’s disease) underwent three EBS applications per week to both the cerebral cortex and auricular-specific sites for a total of 5 weeks. At baseline, after 2 weeks and 5 weeks, a neuropsychological assessment was performed through mini–mental state examination, free and cued selective reminding tests, and trail making test. As secondary outcomes, changes in behavior, functionality, and quality of life were also evaluated. Results After 5 weeks of standardized EBS therapy, significant improvements were observed in all neurocognitive assessments. Mini–mental state examination score significantly increased from baseline to end treatment (+3.19, P=0.002). Assessment of episodic memory showed an improvement both in immediate and delayed recalls (immediate recall =+7.57, P=0.003; delayed recall =+4.78, P<0.001). Executive functions significantly improved from baseline to end stimulation (trail making test A −53.35 seconds; P=0.001). Of note, behavioral disorders assessed through neuropsychiatric inventory significantly decreased (−28.78, P<0.001). The analysis concerning the Alzheimer’s disease and mild cognitive impairment group confirmed a significant improvement of

  3. Design of and rationale for the Japan Diabetes Optimal Integrated Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3): a multicenter, open-label, randomized, parallel-group trial

    PubMed Central

    Ueki, Kohjiro; Sasako, Takayoshi; Kato, Masayuki; Okazaki, Yukiko; Okahata, Sumie; Katsuyama, Hisayuki; Haraguchi, Mikiko; Morita, Ai; Ohashi, Ken; Hara, Kazuo; Morise, Atsushi; Izumi, Kazuo; Ohashi, Yasuo; Noda, Mitsuhiko; Kadowaki, Takashi

    2016-01-01

    Objective Multifactorial intervention including the management of levels of blood glucose (BG), blood pressure (BP), and lipids has been suggested to decrease cardiovascular disease (CVD) risk. However, the target ideal and feasible levels for these individual parameters have not been fully evaluated. In this study, we examine the hypothesis that stricter control compared with the current targets in the Japanese guideline for BG, BP, and lipids could efficiently and safely reduce CVD risk. Research Design and Methods We screened patients with type 2 diabetes and hypertension and/or dyslipidemia among 81 hospitals in Japan and allocated them into 2 groups: the intensive therapy group (ITG) and the conventional therapy group (CTG). For the 2 respective groups, the target for glycated hemoglobin (HbA1c) is <6.2% (44 mmol/mol) and <6.9% (52 mmol/mol), for BP it is <120/75 mm Hg and <130/80 mm Hg, and for low-density lipoprotein cholesterol it is <80 mg/dL (<70 mg/dL in the presence of CVD history) and <120 mg/dL (<100 mg/dL in the presence of CVD history). The primary end point is the occurrence of CVD events or death by any cause. These patients are scheduled for stepwise intensifications of medication for BG, BP, and lipid control in the ITG, until the number of primary end point events reaches 250. Results We recruited 2542 patients and randomly allocated 1271 into the ITG and 1271 into the CTG between June 2006 and March 2009. The mean HbA1c was 8.0% (64 mmol/mol) and the mean duration of diabetes was 8.3 years. Conclusions This randomized controlled study will test the hypothesis that strict multifactorial intervention therapy is effective for the prevention of CVDs in patients with type 2 diabetes who are at high CVD risk. Trial registration number NCT00300976. PMID:26843962

  4. A single centre, open-label, cross-over study of pharmacokinetics comparing topical zinc/clindamycin gel (Zindaclin) and topical clindamycin lotion (Dalacin T) in subjects with mild to moderate acne.

    PubMed

    Chassard, Didier; Kanis, Roo; Namour, Florence; Evene, Eric; Ntssikoussalabongui, Bernard; Schmitz, Valérie

    2006-01-01

    Zinc/clindamycin gel (Zindaclin 1%) gel, is a new once-daily topical acne treatment (Strakan Ltd) containing clindamycin phosphate equivalent to 1% clindamycin and zinc acetate in a formulation, which leads to a reduced systemic absorption of clindamycin through the skin. The objective of the study was to compare the systemic absorption of clindamycin from zinc/clindamycin gel and clindamycin lotion (Dalacin T topical lotion, Pharmacia Ltd) after repeated twice-daily topical administration for two periods of 5 days with an intervening gap of 2 weeks in 24 subjects with mild to moderate acne. Plasma Cmax, and AUC0-12 of clindamycin measured after single and multiple applications of zinc/clindamycin gel were between 30% and 50% lower than for clindamycin lotion. As zinc/clindamycin gel is a topical treatment for acne, the lower systemic bioavailability may be beneficial because there may be a correspondingly lower risk of systemic events in zinc/clindamycin gel-treated subjects.

  5. A European multicentre and open-label controlled randomized trial to evaluate the efficacy of Sequential treatment with TAcrolimus–Rituximab versus steroids plus cyclophosphamide in patients with primary MEmbranous Nephropathy: the STARMEN study

    PubMed Central

    Rojas-Rivera, Jorge; Fernández-Juárez, Gema; Ortiz, Alberto; Hofstra, Julia; Gesualdo, Loreto; Tesar, Vladimir; Wetzels, Jack; Segarra, Alfons; Egido, Jesus; Praga, Manuel

    2015-01-01

    Background Patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome have a high risk of progression to end-stage renal disease. The Ponticelli protocol (steroids with alkylating agents) is the most effective immunosuppressive therapy for this condition, but it has severe adverse effects. Tacrolimus and rituximab have demonstrated efficacy for remission of nephrotic syndrome in MN with a safer profile. However, the published evidence is largely based on small or short-term observational studies, historical cohorts, comparisons with conservative therapy or clinical trials without appropriate control groups, and there is no head-to-head comparison with the Ponticelli protocol. Methods The STARMEN randomized clinical trial will compare the efficacy of sequential tacrolimus–rituximab therapy with a modified Ponticelli protocol (steroids plus cyclophosphamide). The trial will also evaluate the role of antibodies against the M-type phospholipase A2 receptor (anti-PLA2R) and other antibodies as markers of response to treatment and long-term prognosis. Results The trial has already started with 23 patients having been enrolled as of 1 April 2015, an estimated 21.7% of the estimated sample. PMID:26413273

  6. Efficacy and safety profile of combination of tramadol-diclofenac versus tramadol-paracetamol in patients with acute musculoskeletal conditions, postoperative pain, and acute flare of osteoarthritis and rheumatoid arthritis: a Phase III, 5-day open-label study

    PubMed Central

    Chandanwale, Ajay S; Sundar, Subramanian; Latchoumibady, Kaliaperumal; Biswas, Swati; Gabhane, Mukesh; Naik, Manoj; Patel, Kamlesh

    2014-01-01

    Objective We aimed to evaluate the safety and efficacy of a fixed-dose combination (FDC) of tramadol and diclofenac versus a standard approved FDC of tramadol and paracetamol, in patients with acute moderate to severe pain. Methods A total of 204 patients with moderate to severe pain due to acute musculoskeletal conditions (n=52), acute flare of osteoarthritis (n=52), acute flare of rheumatoid arthritis (n=50), or postoperative pain (n=50) were enrolled in the study at baseline. Each disease category was then randomized to receive either of two treatments for 5 days: group A received an FDC of immediate-release tramadol hydrochloride (50 mg) and sustained-release diclofenac sodium (75 mg) (one tablet, twice daily), and group B received an FDC of tramadol hydrochloride (37.5 mg) and paracetamol (325 mg) (two tablets every 4–6 hours, up to a maximum of eight tablets daily). The primary efficacy end points were reductions in pain intensity from baseline at day 3 and day 5 as assessed by a Visual Analog Scale (VAS) score. Results Group A showed a significant reduction in the VAS score for overall pain from baseline on day 3 (P=0.001) and day 5 (P<0.0001) as compared with group B. The combination of tramadol-diclofenac resulted in few mild to moderate adverse events (nausea, vomiting, epigastric pain, and gastritis), which required minimal management, without any treatment discontinuation. The number of adverse events in group A was nine (8.82%) compared with 22 (21.78%) in group B, after 5 days of treatment. Conclusion An FDC of tramadol-diclofenac showed a significantly greater reduction in pain intensity and was well tolerated compared with tramadol-paracetamol, resulting in better analgesia in patients suffering from moderate to severe pain due to acute musculoskeletal conditions, postoperative pain following orthopedic surgery, or acute flare of osteoarthritis and rheumatoid arthritis. PMID:25152629

  7. Multicentre, open-label, randomised, parallel-group, superiority study to compare the efficacy of octreotide therapy 40 mg monthly versus standard of care in patients with refractory anaemia due to gastrointestinal bleeding from small bowel angiodysplasias: a protocol of the OCEAN trial

    PubMed Central

    van Geenen, E J M; Drenth, J P H

    2016-01-01

    Introduction Gastrointestinal angiodysplasias are an important cause of difficult-to-manage bleeding, especially in older patients. Endoscopic coagulation of angiodysplasias is the mainstay of treatment, but may be difficult for small bowel angiodysplasias because of the inability to reach them for endoscopic intervention. Some patients are red blood cell (RBC) transfusion dependent due to frequent rebleeding despite endoscopic treatment. In small cohort studies, octreotide appears to decrease the number of bleeding episodes in patients with RBC transfusion dependency due to gastrointestinal angiodysplasias. This trial will assess the efficacy of octreotide in decreasing the need for RBC transfusions and parenteral iron in patients with anaemia due to gastrointestinal bleeding of small bowel angiodysplasias despite endoscopic intervention. Study design Randomised controlled, superiority, open-label multicentre trial. Participants 62 patients will be included with refractory anaemia due to small bowel angiodysplasias, who are RBC transfusion or iron infusion dependent despite endoscopic intervention and oral iron supplementation. Intervention Patients will be randomly assigned (1:1) to standard care or 40 mg long-acting octreotide once every 4 weeks for 52 weeks, in addition to standard care. The follow-up period is 8 weeks. Main outcome measures The primary outcome is the difference in the number of blood and iron infusions between the year prior to inclusion and the treatment period of 1 year. Important secondary outcomes are the per cent change in the number of rebleeds from baseline to end point, adverse events and quality of life. Ethics and dissemination The trial received ethical approval from the Central Committee on Research Involving Human Subjects and from the local accredited Medical Research Ethics Committee of the region Arnhem-Nijmegen, the Netherlands (reference number: 2014-1433). Results will be published in a peer-reviewed journal and

  8. A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide

    PubMed Central

    Setnik, Beatrice; Roland, Carl L; Sommerville, Kenneth W; Pixton, Glenn C; Berke, Robert; Calkins, Anne; Goli, Veeraindar

    2015-01-01

    Objective To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN) using a standardized conversion guide. Methods This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Results Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%). The mean (standard deviation) number of days to stable dose was 20 (8.94), and number of titration steps to stable dose was 2.4 (1.37). The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conclusion Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN. PMID:26185466

  9. Individual, physical and psychological risk factors for neck pain in Australian office workers: a 1-year longitudinal study.

    PubMed

    Hush, Julia M; Michaleff, Zoe; Maher, Christopher G; Refshauge, Kathryn

    2009-10-01

    Neck pain is more prevalent in office workers than in the general community. To date, findings from prospective studies that investigated causal relationships between putative risk factors and the onset of neck pain in this population have been limited by high loss to follow-up. The aim of this research was to prospectively evaluate a range of risk factors for neck pain in office workers, using validated and reliable objective measures as well as attain an estimate of 1-year incidence. We assembled a cohort of 53 office workers without neck pain and measured individual, physical, workplace and psychological factors at baseline. We followed participants for 1 year to measure the incidence of neck pain. We achieved 100% participant follow-up. Cox regression analysis was applied to examine the relationship between the putative risk factors and the cumulative incidence of neck pain. The 1-year incidence proportion of neck pain in Australian office workers was estimated in this study to be 0.49 (95% CI 0.36-0.62). Predictors of neck pain with moderate to large effect sizes were female gender (HR: 3.07; 95% CI: 1.18-7.99) and high psychological stress (HR: 1.64; 95% CI: 0.66-4.07). Protective factors included increased mobility of the cervical spine (HR: 0.44; 95% CI: 0.19-1.05) and frequent exercise (HR: 0.64; 95% CI: 0.27-1.51). These results reveal that neck pain is common in Australian office workers and that there are risk factors that are potentially modifiable.

  10. Acupuncture and occlusal splint therapy in the treatment of craniomandibular disorders. II. A 1-year follow-up study.

    PubMed

    List, T; Helkimo, M

    1992-12-01

    Eighty patients, of whom 22 were men and 58 women, participated in a 1-year follow-up study. All participants in the study showed signs and symptoms of craniomandibular disorders (CMD) and had had pain for more than 6 months at treatment start. The patients were randomly assigned to either acupuncture or occlusal splint therapy. Those patients who did not respond to either of the treatment modes were offered various additional therapies. The result showed that 57% of the patients who received acupuncture and 68% of the patients treated with occlusal splint therapy benefited subjectively (p < 0.01) and clinically (p < 0.001) from the treatment over a 12-month period. No statistically significant difference was found between the two groups as to the assessment variables. Those patients who received various additional therapies after acupuncture and/or occlusal splint therapy responded favorably to additional treatment in only a few instances. The study showed that acupuncture gave positive results similar to those of occlusal splint therapy in patients with primarily myogenic CMD symptoms over a 1-year follow-up period.

  11. Cognitive function, social functioning and quality of life in first-episode psychosis: A 1-year longitudinal study.

    PubMed

    Popolo, Raffaele; Vinci, Giancarlo; Balbi, Andrea

    2010-03-01

    Abstract Objective. The majority of patients with schizophrenia have cognitive deficits early in the disease. We evaluated the relationship between cognitive function, social functioning and quality of life in patients with first-episode psychosis. Methods. This was a longitudinal study in 15 patients aged 18-30 years who had recently experienced a first psychotic episode and were treated with the atypical antipsychotic aripiprazole, cognitive-behavioural therapy, psycho-educational sessions, family supportive sessions and social interventions. Patients were evaluated at baseline and after 1 year. Cognitive assessment included attention, memory, language skills and problem solving. Social functioning, quality of life, and psychopathological evaluation were performed with validated tools. Results. At baseline, patients had a severe impairment of social functioning and a low quality of life, while a specific pattern of cognitive functions was not identified. After 1-year, we observed a significant improvement in social functioning and quality of life, without a significant decrease in cognitive function. Conclusion. Contrary to previous findings, we found that social functioning and quality of life are related, but independent of cognitive impairment. The use of antipsychotic agents that do not interefere with cognitive function plus psychological assistance is a valuable treatment approach in patients with first-episode schizophrenia.

  12. Time to First Shunt Failure in Pediatric Patients over 1 Year Old: A 10-Year Retrospective Study.

    PubMed

    Shannon, Chevis N; Carr, Kevin R; Tomycz, Luke; Wellons, John C; Tulipan, Noel

    2013-01-01

    Studies comparing alternatives to ventriculoperitoneal (VP) shunting for treatment of hydrocephalus have often relied upon data from an earlier era that may not be representative of contemporary shunt survival outcomes. We sought to determine the shunt survival rate of our cohort and compare our results to previously published shunt survival and endoscopic third ventriculostomy (ETV) success rates. We identified 95 patients between 1 and 18 years of age, who underwent initial VP shunt placement between January 2001 and December 2010. Our study shows a shunt survival rate of 85% at 6 months and 79% at 2 years, for initial shunts in pediatric patients over 1 year of age in this cohort. The overall infection rate was 3%. This compares favorably with published success rates of ETV at similar time points as well as with the rate of infection. This suggests that ventricular shunting remains a viable alternative to ETV in the older child.

  13. Risk and protective factors for peer victimization: a 1-year follow-up study of urban American students.

    PubMed

    Karlsson, Elisabeth; Stickley, Andrew; Lindblad, Frank; Schwab-Stone, Mary; Ruchkin, Vladislav

    2014-09-01

    This study examined whether internalizing problems, parental warmth and teacher support were associated with adolescents' experience of future peer victimization in school. Data were drawn from two rounds of the longitudinal Social and Health Assessment (SAHA). Study subjects comprised 593 US urban adolescents (aged 13.8 ± 0.8 years; 56 % female). Results showed that there was a substantial degree of continuity in peer victimization over a 1-year period. The presence of internalizing (anxiety, depressive and somatic) symptoms at baseline was associated with an increased risk of peer victimization over time. Both parental warmth and teacher support were uniquely associated with a lower risk for peer victimization. Implications of these findings for prevention efforts are discussed.

  14. Adjunctive lisdexamfetamine dimesylate therapy in adult outpatients with predominant negative symptoms of schizophrenia: open-label and randomized-withdrawal phases.

    PubMed

    Lasser, Robert A; Dirks, Bryan; Nasrallah, Henry; Kirsch, Courtney; Gao, Joseph; Pucci, Michael L; Knesevich, Mary A; Lindenmayer, Jean-Pierre

    2013-10-01

    Negative symptoms of schizophrenia (NSS), related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex, are predictive of poor outcomes and have no effective treatment. Use of dopamine-enhancing drugs (eg, psychostimulants) has been limited by potential adverse effects. This multicenter study examined lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, as adjunctive therapy to antipsychotics in adults with clinically stable schizophrenia and predominant NSS. Outpatients with stable schizophrenia, predominant NSS, limited positive symptoms, and maintained on stable atypical antipsychotic therapy underwent a 3-week screening, 10-week open-label adjunctive LDX (20-70 mg/day), and 4-week, double-blind, randomized, placebo-controlled withdrawal. Efficacy measures included a modified Scale for the Assessment of Negative Symptoms (SANS-18) and Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Ninety-two participants received open-label LDX; 69 received double-blind therapy with placebo (n=35) or LDX (n=34). At week 10 (last observation carried forward; last open-label visit), mean (95% confidence interval) change in SANS-18 scores was -12.9 (-15.0, -10.8; P<0.0001). At week 10, 52.9% of participants demonstrated a minimum of 20% reduction from baseline in SANS-18 score. Open-label LDX was also associated with significant improvement in PANSS total and subscale scores. During the double-blind/randomized-withdrawal phase, no significant differences (change from randomization baseline) were found between placebo and LDX in SANS-18 or PANSS subscale scores. In adults with clinically stable schizophrenia, open-label LDX appeared to be associated with significant improvements in negative symptoms without positive symptom worsening. Abrupt LDX discontinuation was not associated with positive or negative symptom worsening. Confirmation with larger controlled trials is warranted. PMID:23756608

  15. Single Versus Multi-visit Endodontic Treatment of Teeth with Apical Periodontitis: An in vivo Study with 1-year Evaluation

    PubMed Central

    Gill, GS; Bhuyan, AC; Kalita, C; Das, L; Kataki, R; Bhuyan, D

    2016-01-01

    Background: Apical periodontitis (AP) is one of the most prevalent diseases of the teeth. Treatment of AP is based on the removal of the cause, i.e., bacteria from the root canals. Achievement of adequate bacterial eradication in one appointment treatment remains a controversy. Aim: This prospective study was conducted with the objective to compare the periapical healing of teeth with AP treated in (a) single visit versus (b) two visits, either with or without Vitapex as an intracanal medicament. Subjects and Methods: Patients were selected randomly from the Department of Conservative Dentistry and Endodontics. Forty-three patients (81 teeth) met the inclusion criteria, i.e., AP (both symptomatic and asymptomatic) visible radiographically size ≥2 mm × 2 mm, not suffering from any immune-compromising disease, age between 16 and 65 years and tooth not accessed previously. Patients were randomly divided into three groups, i.e., single-visit group (Group 1), multi-visit group without any intracanal medicament (Group 2), and multi-visit group with Vitapex as interim intracanal medicament (Group 3). Comparison was done radiographically using periapical index (PAI). The primary outcome measure was the change in periapical radiolucency after 1 year assessed by PAI scores. The Mann-Whitney U-test was used to evaluate differences between groups at baseline (immediate postoperative) and at the 12-month follow-up evaluation. Change in PAI score for each group from baseline to 12-month follow-up evaluation was tested with the Wilcoxon signed rank test. The secondary outcome measures, proportion of teeth in each group that could be considered improved (decreased PAI score) or healed (PAI <2), were assessed with the Chi-square test. Results: No statistically significant difference in periapical healing was found between three groups. Conclusion: After 1-year evaluation, no difference in periapical healing was found between single-visit treatment and multi-visit treatment

  16. A longitudinal study on the osteoarthritic change of the temporomandibular joint based on 1-year follow-up computed tomography.

    PubMed

    Lee, Jeong-Yun; Kim, Dae-Jung; Lee, Sang-Goo; Chung, Jin-Woo

    2012-12-01

    This study aims to report the results of a 1-year computed tomographic (CT) follow up of 54 temporomandibular joints (TMJs) affected by osteoarthritis (OA) and to provide longitudinal information on changes in OA and its relationship with clinical signs and symptoms. TMJ OA was diagnosed by history, clinical and CT examinations. The second CT examination was done after about 1 year of conservative treatment. Joints were divided into three groups labeled as no change, improved CT, and worsened CT groups depending on the longitudinal bony change of OA observed in the CT. The sex distribution, mean age, joint noise, subjective pain, joint tenderness, masticatory muscle tenderness, and improvement of subjective symptoms were not different between the groups at the first and second examination, while maximum (p < 0.01) and painless mouth opening range (p < 0.001) at the first examination were both smaller in the worsened CT group. Although the clinical signs and symptoms of OA were improved in 40 joints, 74.1%, at 7.2 ± 4.6 months, the amount if improvement did not differ between the groups. The extent of the destructive change of the condyle was highest in the improved CT group at the first (p < 0.001) and in the worsened CT group at the second examination (p < 0.001). These results imply that the prognosis of OA changes may be independent of the clinical signs and symptoms. More specific longitudinal information as regards OA changes of the TMJ based on a larger sample and a longer follow-up period would be likely to provide a better understanding of TMJ OA. PMID:22075324

  17. Persistence of immune responses to the HPV-16/18 AS04-adjuvanted vaccine in women aged 15–55 years and first-time modelling of antibody responses in mature women: results from an open-label 6–year follow-up study

    PubMed Central

    Schwarz, T; Spaczynski, M; Kaufmann, A; Wysocki, J; Gałaj, A; Schulze, K; Suryakiran, P; Thomas, F; Descamps, D

    2015-01-01

    Objective Evaluation of the long-term HPV-16/18 AS04-adjuvanted vaccine immunogenicity persistence in women. Design Multicentre, open-label, long-term follow-up (NCT00947115) of a primary phase–III study (NCT00196937). Setting Six centres in Germany and Poland. Population 488 healthy women (aged 15–55 years, age-stratified into groups: 15–25, 26–45, and 46–55 years) who received three vaccine doses in the primary study. Methods Immune responses were evaluated in serum and cervicovaginal secretion (CVS) samples 6 years after dose 1. Anti-HPV-16/18 geometric mean titres (GMTs) were measured by enzyme-linked immunosorbent assay (ELISA), and were used to fit the modified power-law and piecewise models, predicting long-term immunogenicity. Serious adverse events (SAEs) were recorded. Main outcome measures Anti-HPV-16/18 seropositivity rates and GMTs 6 years after dose 1. Results At 6 years after dose 1, all women were seropositive for anti-HPV–16 and ≥97% were seropositive for anti-HPV–18 antibodies. GMTs ranged from 277.7 to 1344.6 EU/ml, and from 97.6 to 438.2 EU/ml, for anti-HPV–16 and anti-HPV–18, respectively. In all age groups, GMTs were higher (anti-HPV–16, 9.3–45.1-fold; anti-HPV–18, 4.3–19.4-fold) than levels associated with natural infection (29.8 EU/ml). A strong correlation between serum and CVS anti-HPV-16/18 levels was observed, with correlation coefficients of 0.81–0.96 (anti-HPV–16) and 0.69–0.84 (anti-HPV–18). Exploratory modelling based on the 6–year data predicted vaccine-induced anti-HPV-16/18 levels above natural infection levels for at least 20 years, except for anti-HPV–18 in the older age group (piecewise model). One vaccine-related and two fatal SAEs were reported. Conclusions At 6 years after vaccination, immune responses induced by the HPV-16/18 AS04-adjuvanted vaccine were sustained in all age groups. PMID:25208608

  18. Young male soccer players exhibit additional bone mineral acquisition during the peripubertal period: 1-year longitudinal study.

    PubMed

    Zouch, Mohamed; Vico, Laurence; Frere, Delphine; Tabka, Zouhair; Alexandre, Christian

    2014-01-01

    The aim of this study was to determine whether soccer could have different bone benefits in prepubescent and pubescent boys. We investigated 76 boys aged 10 to 13 years during a 1-year study. All boys were prepubescent at the beginning of the study (T0); pubescent status was determined by a complete 24-h urine hormonal assay of FSH-LH, with LH ≤ 0.31 IU/24 h and FSH ≤ 2.19 IU/24 h corresponding to prepubescent Tanner stage I and with 0.31 < LH < 0.95 IU/24 h and 1.57 < FSH < 3.77 IU/24 h corresponding to pubescent Tanner stage II. At the end of the study (T1), 35 boys remained prepubescent (22 soccer players (F1) and 13 controls (C1)), and 41 boys had entered puberty (26 soccer players (F2) and 15 controls (C2)). Soccer players completed 2 to 5 h of training plus one competition game per week during the school year, and controls only had physical education at school. Bone mineral content (BMC) was measured at T0 and T1 by DPX in the lumbar spine, total hip, and whole body (WB) for a comparison between soccer players and controls. At T0, no BMC difference was found between F1 and C1, but BMC was higher in F2 than C2 in WB and weight-bearing sites. At T1, BMC was higher in WB and weight-bearing sites in both F1 and F2 compared to their respective controls. Between T0 and T1, soccer induced a BMC gain at weight-bearing sites in both F1 and F2 compared to C1 and C2, respectively. The soccer-related bone gain was greater in WB and weight-bearing (the lumbar spine, total hip, and supporting leg) and non-weight-bearing bones (dominant arm and nondominant arm) in boys who became pubescent than in boys who remained prepubescent. In conclusion, 1-year study in young male soccer players demonstrates that the process of bone accretion at the very early phase of puberty is more intensely stimulated by the combination of physical exercise and sexual impregnation than by one of these factors alone.

  19. Predictors of Poststroke Health-Related Quality of Life in Nigerian Stroke Survivors: A 1-Year Follow-Up Study

    PubMed Central

    Hamza, Ashiru Mohammad; Al-Sadat, Nabilla; Loh, Siew Yim; Jahan, Nowrozy Kamar

    2014-01-01

    This study aims to identify the predictors in the different aspects of the health-related quality of life (HRQoL) and to measure the changes of functional status over time in a cohort of Nigerian stroke survivors. A prospective observational study was conducted in three hospitals of Kano state of Nigeria where stroke survivors receive rehabilitation. The linguistic-validated Hausa versions of the stroke impact scale 3.0, modified Rankin scale, Barthel index and Beck depression inventory scales were used. Paired samples t-test was used to calculate the amount of changes that occur over time and the forward stepwise linear regression model was used to identify the predictors. A total of 233 stroke survivors were surveyed at 6 months, and 93% (217/233) were followed at 1 year after stroke. Functional disabilities were significantly reduced during the recovery phase. Motor impairment, disability, and level of depression were independent predictors of HRQoL in the multivariate regression analysis. The involvement of family members as caregivers is the key factor for those survivors with improved functional status. Thus, to enhance the quality of poststroke life, it is proposed that a holistic stroke rehabilitation service and an active involvement of family members are established at every possible level. PMID:24982864

  20. Functional disability in medication management and driving among individuals with HIV: a 1-year follow-up study.

    PubMed

    Thames, April D; Arentoft, Alyssa; Rivera-Mindt, Monica; Hinkin, Charles H

    2013-01-01

    Approximately 50% of individuals with HIV report cognitive deficits that can affect social or occupational functioning. The present study used a longitudinal design (1 year) to examine the relationship between cognitive factors and incidental functional deficits in medication management and driving ability among a cohort of 101 HIV+ participants. Participants were classified into groups of functionally "stable" and "disabled" for each laboratory-based functional task (i.e., Medication Management Task-Revised, MMT-R, and PC-based driving simulator). We hypothesized that participants who exhibited a functional deficit in either MMT-R or driving at follow-up assessment would demonstrate significantly poorer baseline cognitive performance at study entry than participants who remained functionally stable. As hypothesized, participants who demonstrated significantly lower baseline performance in learning/memory and executive functioning also demonstrated functional disability on the MMT-R at follow-up when compared to functionally stable participants. Poor baseline performance in speed of information processing was associated with a deficit in driving ability at follow-up assessment. Our results suggest that lower baseline cognitive functioning predicts downstream functional disability, and that deficits in learning/memory and information processing speed are particularly predictive of deficits in medication management and driving ability.

  1. Effect of monochloramine treatment on colonization of a hospital water distribution system by Legionella spp.: a 1 year experience study.

    PubMed

    Mancini, Benedetta; Scurti, Maria; Dormi, Ada; Grottola, Antonella; Zanotti, Andrea; Cristino, Sandra

    2015-04-01

    Contamination of hot water distribution systems by Legionella represents a great challenge due to difficulties associated with inactivating microorganisms, preserving the water characteristics. The aim of this study was to examine over the course of 1 year in 11 fixed sites, the impact of monochloramine disinfection on Legionella, heterotrophic bacteria (36 °C), Pseudomonas aeruginosa contamination, and chemical parameters of a plumbing system in an Italian hospital. Three days after installation (T0), in the presence of monochloramine concentration between 1.5 and 2 mg/L, 10/11 sites (91%) were contaminated by L. pneumophila serogroups 3 and 10. After these results, the disinfectant dosage was increased to between 6 and 10 mg/L, reducing the level of Legionella by three logarithmic unit by 2 months postinstallation (T2) until 6 months later (T3). One year later (T4), there was a significant reduction (p = 0.0002) at 8/11 (73%) sites. Our data showed also a significant reduction of heterotrophic bacteria (36 °C) in 6/11 (55%) sites at T4 (p = 0.0004), by contrast the contamination of P. aeruginosa found at T0 in two sites persisted up until T4. The results of the present study show that monochloramine is a promising disinfectant that can prevent Legionella contamination of hospital water supplies.

  2. An Open-Label Trial of Memantine for Cognitive Impairment in Patients with Posttraumatic Stress Disorder

    PubMed Central

    Ramaswamy, Sriram; Madabushi, Jayakrishna; Hunziker, John; Bhatia, Subhash C.; Petty, Frederick

    2015-01-01

    Background. Studies using standard neuropsychological instruments have demonstrated memory deficits in patients with PTSD. We evaluated the efficacy and safety of the N-methyl-D-aspartate antagonist memantine in veterans with PTSD and cognitive impairment. Methods. Twenty-six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open-label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS measures attention, language, visuospatial skills, and immediate and delayed memories. The Clinician Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan Disability Scale (SDS) were secondary outcome measures. Results. There was a significant improvement in RBANS, both total and subscale scores (P < 0.05), over time. There was a reduction in total CAPS scores, avoidance/numbing symptoms (CAPS-C) and hyperarousal symptoms (CAPS-D), HAM-D, Q-LES-Q, and SDS scores. However, there was no reduction in reexperiencing (CAPS-B) and HAM-A scores. Memantine was well tolerated. Conclusions. Memantine improved cognitive symptoms, PTSD symptoms, and mood in veterans with PTSD. Randomized double-blind studies are needed to validate these preliminary observations. PMID:26064685

  3. Cinnarizine in migraine prophylaxis: efficacy, tolerability and predictive factors for therapeutic responsiveness. An open-label pilot trial.

    PubMed

    Rossi, Paolo; Fiermonte, Giancarlo; Pierelli, Francesco

    2003-01-01

    The efficacy and tolerability of cinnarizine (75 mg, at bedtime) in migraine prophylaxis and the presence of possible predictive factors for therapeutic responsiveness were evaluated in an open-label pilot trial. Eighty consecutive outpatients suffering from migraine with or without aura participated in the study. After 12 weeks of therapy, 55 patients experienced a greater than 66% reduction in headache frequency and were considered responders. A significant reduction in the number of migraine days (mean reduction 58 +/- 8%) and in intake of medication to treat acute attacks (mean reduction 55 +/- 11%) was also observed. Cinnarizine was well tolerated, as documented by the low number of adverse effects. Failure to respond to previous prophylactic treatments was a negative predictive factor correlated with a poor prognosis. This study, even bearing in mind its limitations as an open-label trial, suggests that cinnarizine might be an effective prophylactic anti-migraine agent. The clinical characteristics of migraine patients do not help to predict response to treatment. PMID:14703897

  4. Maternal Music Exposure during Pregnancy Influences Neonatal Behaviour: An Open-Label Randomized Controlled Trial

    PubMed Central

    Arya, Ravindra; Chansoria, Maya; Konanki, Ramesh; Tiwari, Dileep K.

    2012-01-01

    Objective. This study evaluated the effect of antenatal music exposure to primigravida healthy mothers on the behaviour of their term appropriate-for-date newborns assessed using Brazelton Neonatal Behavioral Assessment Scale (BNBAS). Methods. This was a single-centre, randomized, open-label controlled trial. Primigravida mothers aged 19–29 years, free of chronic medical diseases or significant deafness, with singleton pregnancy, with a gestation of 20 weeks or less, were randomized to listen to a pre-recorded music cassette for approximately 1 hour/day in addition to standard antenatal care (intervention arm) or standard care only (control arm). Perinatal factors with adverse effect on neonatal behaviour were deemed as protocol violations. Outcome measure included scores on 7 clusters of BNBAS. Primary analysis was per protocol. The trial is registered with ClinicalTrials.gov (NCT01278329). Results. One hundred and twenty-six newborns in the music group and 134 in the control group were subjected to BNBAS assessment. The infants of mothers exposed to music during pregnancy performed significantly better on 5 of the 7 BNBAS clusters. The maximal beneficial effect was seen with respect to orientation (ES 1.13, 95% CI 0.82–1.44, P < 0.0001) and habituation (ES 1.05, 95% CI 0.53–1.57, P = 0.0001). Conclusion. Prenatal music exposure to mother significantly and favourably influences neonatal behaviour. PMID:22518187

  5. Impact of a soy drink on climacteric symptoms: an open-label, crossover, randomized clinical trial

    PubMed Central

    Tranche, Salvador; Brotons, Carlos; Pascual de la Pisa, Beatriz; Macías, Ramón; Hevia, Eduardo; Marzo-Castillejo, Mercè

    2016-01-01

    Abstract Objectives: The objective of this study is to evaluate the effects of a soy drink with a high concentration of isoflavones (ViveSoy®) on climacteric symptoms. Methods: An open-label, controlled, crossover clinical trial was conducted in 147 peri- and postmenopausal women. Eligible women were recruited from 13 Spanish health centers and randomly assigned to one of the two sequence groups (control or ViveSoy®, 500 mL per day, 15 g of protein and 50 mg of isoflavones). Each intervention phase lasted for 12 weeks with a 6-week washout period. Changes on the Menopause Rating Scale and quality of life questionnaires, as well as lipid profile, cardiovascular risk and carbohydrate and bone metabolism were assessed. Statistical analysis was performed using a mixed-effects model. Results: A sample of 147 female volunteers was recruited of which 90 were evaluable. In both sequence groups, adherence to the intervention was high. Regular consumption of ViveSoy® reduced climacteric symptoms by 20.4% (p = 0.001) and symptoms in the urogenital domain by 21.3% (p < 0.05). It also improved health-related quality life by 18.1%, as per the MRS questionnaire (p <0.05). Conclusion: Regular consumption of ViveSoy® improves both the somatic and urogenital domain symptoms of menopause, as well as health-related quality of life in peri- and postmenopausal women. PMID:26806546

  6. Effect of 1-year regular Tai Chi on neuromuscular reaction in elderly women: a randomized controlled study.

    PubMed

    Sun, Wei; Zhang, Cui; Song, Qipeng; Li, Weiping; Cong, Yan; Chang, Shuwan; Mao, Dewei; Hong, Youlian

    2016-01-01

    This study assessed the effect of 1-year regular Tai Chi (TC) on neuromuscular reaction in elderly women. A total of 41 elderly women (55 years-68 years) completed the study. The TC group (n = 21) performed the 24-form TC, while the control group (C, n = 20) was instructed to read newspapers or watch television when the TC group practised. Electromyogram measurements were conducted before and after intervention. After a year-long intervention, the post-test results of between-group neuromuscular reaction time showed significant differences in the rectus femoris (t = 3.607, p = 0.001), semitendinosus (t = 2.678, p = 0.011), anterior tibialis (t = 3.455, p = 0.001), and gastrocnemius muscles (t = 4.061, p = 0.000). Within-group results showed that the TC group had significantly shorter neuromuscular reaction time compared to its baseline value in the rectus femoris (t = 3.066, p = 0.006), semitendinosus (t = 2.485, p = 0.022), anterior tibialis (t = 2.311, p = 0.032), and gastrocnemius muscles (t = 2.462, p = 0.023). Results suggested that year-long regular TC can improve neuromuscular reaction function in elderly women.

  7. Influence of CT utilisation on patient flow in the emergency department: a retrospective 1-year cohort study

    PubMed Central

    Li, Chao-Jui; Syue, Yuan-Jhen; Lin, Yan-Ren; Cheng, Hsien-Hung; Cheng, Fu-Jen; Tsai, Tsung-Cheng; Chen, Kuan-Fu; Lee, Chien-Hung

    2016-01-01

    Objective CT, an important diagnostic tool in the emergency department (ED), might increase the ED length of stay (LOS). Considering the issue of ED overcrowding, it is important to evaluate whether CT use delays or facilitates patient disposition in the ED. Design A retrospective 1-year cohort study. Setting 5 EDs within the same healthcare system dispersed nationwide in Taiwan. Participants All adult non-trauma patients who visited the 5 EDs from 1 July 2011 to 30 June 2012. Interventions Patients were grouped by whether or not they underwent a CT scan (CT and non-CT groups, respectively). Primary and secondary outcome measures The ED LOS and hospital LOS between patients who had and had not undergone CT scans were compared by stratifying different dispositions and diagnoses. Results CT use prolonged patient ED LOS among those who were directly discharged from the ED. Among patients admitted to the observation unit and then discharged, patients diagnosed with nervous system disease had shorter ED LOS if they underwent a CT scan. CT use facilitated patient admission to the general ward. CT use also accelerated patients' admission to the intensive care unit (ICU) for patients with nervous system disease, neoplasm and digestive disease. Finally, patients admitted to the general wards had shorter hospital LOS if they underwent CT scans in the ED. Conclusions CT use did not seem to have delayed patient disposition in ED. While CT use facilitated patient disposition if they were finally hospitalised, it mildly prolonged ED LOS in cases of patients discharged from the ED. PMID:27147387

  8. Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

    ERIC Educational Resources Information Center

    McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

    2011-01-01

    Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

  9. A Nutritional Formulation for Cognitive Performance in Mild Cognitive Impairment: A Placebo-Controlled Trial with an Open-Label Extension.

    PubMed

    Remington, Ruth; Lortie, Jevin J; Hoffmann, Heather; Page, Robert; Morrell, Christopher; Shea, Thomas B

    2015-01-01

    Thirty-four individuals with mild cognitive impairment were randomized for 6 months to a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or indistinguishable placebo, followed by a 6-month open-label extension in which all individuals received NF. The NF cohort improved in the Dementia Rating Scale (DRS; effect size >0.7) and maintained baseline performance in CLOX-1. The placebo cohort did not improve in DRS and declined in CLOX-1, but during the open-label extension improved in DRS and ceased declining in CLOX-1. These findings extend prior studies of NF efficacy for individuals without cognitive impairment and with Alzheimer's disease.

  10. A 10-month, open-label evaluation of desvenlafaxine in Japanese outpatients with major depressive disorder.

    PubMed

    Tourian, Karen; Wang, Ying; Ii, Yoichi

    2013-07-01

    The objective of this study was to evaluate the long-term safety of desvenlafaxine for continuation treatment of major depressive disorder (MDD) in Japanese patients. This was a phase 3, multicenter, 10-month, open-label study with flexible dosing of desvenlafaxine (25, 50, 100 mg/day). Japanese patients with MDD who had completed an 8-week, double-blind, placebo-controlled study in which patients received 25 or 50 mg/day desvenlafaxine or placebo were enrolled. In this study, patients received desvenlafaxine 25 mg/day from days 1 to 14, with subsequent upward titration, to a maximum of 100 mg/day, determined by clinical response. Of 304 patients, 75 (24.7%) discontinued during the on-therapy period; patient request was the most common reason (11.5%). Treatment-emergent adverse events were reported by 240 patients (78.9%) during the on-therapy period; the most common adverse events were nasopharyngitis (37.2%), somnolence (11.5%), headache (10.5%), and nausea (10.2%). For the ITT-LOCF population, the mean change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D₁₇) total score was -4.76 (95% confidence interval: -5.47 to -4.05); continued numerical improvements in the HAM-D₁₇ total scores and other depression outcome measures were observed irrespective of treatment in the previous study. Long-term use of desvenlafaxine was safe and well tolerated, with a clinical benefit/risk profile similar to that in other populations.

  11. Nutritional and Safety Outcomes from an Open-Label Micronutrient Intervention for Pediatric Bipolar Spectrum Disorders

    PubMed Central

    Gracious, Barbara; Arnold, L. Eugene; Failla, Mark; Chitchumroonchokchai, Chureeporn; Habash, Diane; Fristad, Mary A.

    2013-01-01

    Abstract Objective The purpose of this study was to report the safety, tolerability, and serum micronutrient concentrations and their correlations with mood changes from an 8 week pilot feasibility study of a 36 ingredient multinutrient supplement, EMPowerplus (EMP+), for pediatric bipolar spectrum disorders (BPSD). Methods Ten children ages 6–12 received EMP+ escalating from one to four capsules t.i.d., with four children increased to the maximum suggested dose, five capsules t.i.d. Outcome measures were micronutrient concentrations in serum and red blood cells, vital signs, body mass index (BMI), dietary intake (Food Frequency Questionnaire and 24 hour dietary recall interview), and mood and global functioning ratings. Results Seven children (70%) completed the study. Three (30%) terminated early for tolerability and compliance issues. Adverse effects were mild and transient, and chiefly consisted of initial insomnia or gastrointestinal (GI) upset. No differences occurred in BMI (p=0.310) or waist–hip ratio (WHR; p=0.674) pre- to postsupplementation. Four of the tested serum vitamin concentrations increased from pre- to postsupplementation: vitamin A-retinol, vitamin B6, vitamin E-α-tocopherol; and folate (all p<0.05). The increase in serum 25-OH vitamin D approached significance (p=0.063). No differences were found in dietary intake pre- to postsupplementation, suggesting that blood nutrient level increases were caused by EMP+. Conclusions In this open prospective study, short-term use of EMP+ in children with BPSD appeared safe and well-tolerated, with a side effect profile preferable to first-line psychotropic drugs for pediatric bipolar spectrum disorders. A double-blind, randomized clinical trial is feasible, appears safe, and is warranted by open-label clinical outcomes and plausible mechanisms of action, combined with documentation of increased serum concentrations of specific micronutrients. PMID:24138009

  12. A pilot open label, single dose trial of fenobam in adults with fragile X syndrome

    PubMed Central

    Berry-Kravis, E; Hessl, D; Coffey, S; Hervey, C; Schneider, A; Yuhas, J; Hutchison, J; Snape, M; Tranfaglia, M; Nguyen, D V; Hagerman, R

    2009-01-01

    Objective: A pilot open label, single dose trial of fenobam, an mGluR5 antagonist, was conducted to provide an initial evaluation of safety and pharmacokinetics in adult males and females with fragile X syndrome (FXS). Methods: Twelve subjects, recruited from two fragile X clinics, received a single oral dose of 50–150 mg of fenobam. Blood for pharmacokinetic testing, vital signs and side effect screening was obtained at baseline and numerous time points for 6 h after dosing. Outcome measures included prepulse inhibition (PPI) and a continuous performance test (CPT) obtained before and after dosing to explore the effects of fenobam on core phenotypic measures of sensory gating, attention and inhibition. Results: There were no significant adverse reactions to fenobam administration. Pharmacokinetic analysis showed that fenobam concentrations were dose dependent but variable, with mean (SEM) peak values of 39.7 (18.4) ng/ml at 180 min after the 150 mg dose. PPI met a response criterion of an improvement of at least 20% over baseline in 6 of 12 individuals (4/6 males and 2/6 females). The CPT did not display improvement with treatment due to ceiling effects. Conclusions: Clinically significant adverse effects were not identified in this study of single dose fenobam across the range of dosages utilised. The positive effects seen in animal models of FXS treated with fenobam or other mGluR5 antagonists, the apparent lack of clinically significant adverse effects, and the potential beneficial clinical effects seen in this pilot trial support further study of the compound in adults with FXS. PMID:19126569

  13. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study

    PubMed Central

    Trotta, Antonella; Murray, Robin M.; David, Anthony S.; Kolliakou, Anna; O’Connor, Jennifer; Di Forti, Marta; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Fisher, Helen L.

    2016-01-01

    While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services. PMID:26373540

  14. Multisite, open-label, prospective trial of lamotrigine for geriatric bipolar depression: a preliminary report

    PubMed Central

    Sajatovic, Martha; Gildengers, Ariel; Jurdi, Rayan K Al; Gyulai, Laszlo; Cassidy, Kristin A; Greenberg, Rebecca L; Bruce, Martha L; Mulsant, Benoit H; Have, Thomas Ten; Young, Robert C

    2013-01-01

    Aims This is a multisite, 12-week, open-label trial of lamotrigine augmentation in 57 older adults (≥ 60 years; mean ± SD age = 66.5 ± 6.7 years) with either type I or type II bipolar depression. Methods Primary outcome measure was change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcome measures included Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression-Bipolar version (CGI-BP), and the WHO-Disability Assessment Schedule II (WHO-DAS II). The Udvalg for Kliniske Undersøgelser (UKU) was used to assess side effects. Results A total of 77.2% of the study subjects had bipolar I disorder. The mean (SD) lamotrigine dose was 150.9 (68.5) mg/day. There was significant improvement in the MADRS, HAM-D, CGI-BP, and in most domains on the WHO-DAS II. For patients for whom final MADRS score was available: 31 (57.4%) met remission criteria and 35 (64.8%) met response criteria. There were 19/57 (33.3%) who dropped out of the study prematurely, with 6 dropouts due to adverse events (4 cases of rash, 1 manic switch, and 1 hyponatremia). Two cases of rash were possibly drug related and were resolved with drug discontinuation. The most common UKU adverse effects were reduced sleep duration (n = 14, 24.6%), weight loss (n = 12, 21.1%), increased dream activity (n = 12, 21.1%), polyuria/polydipsia (n = 11, 19.3%), weight gain (n = 9, 15.8%), diminished sexual desire (n = 9, 15.8%), increased sleep (n = 9, 15.8%), lassitude/fatigue (n = 8, 14%), and unsteady gait (n = 8, 14%). No significant changes in electrocardiogram or laboratory tests were observed. Conclusions In bipolar depressed elders, lamotrigine was associated with improvement in depression, psychopathology, and functional status. There was a moderate number of adverse events, although relationship of adverse events (particularly falls) to study medication could not be clearly determined in this uncontrolled trial. Controlled studies are needed to further

  15. Emotional Reactivity and the Emergence of Conduct Problems and Emotional Symptoms in 7- to 11-Year-Olds: A 1-Year Follow-up Study

    ERIC Educational Resources Information Center

    Sharp, Carla; Petersen, Nancy; Goodyer, Ian

    2008-01-01

    A study to investigate the relation between psychopathology and predictive validity of emotional reactivity in children over a 1-year follow up period was conducted. The investigation was done using the International Affective Picture System to determine individual differences in the emotional and attention process involved in appetitive and…

  16. Rapid Naming in Relation to Reading and Writing in Korean (Hangul), Chinese (Hanja) and English among Korean Children: A 1-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Cho, Jeung-Ryeul; Chiu, Ming Ming

    2015-01-01

    The relation of rapid automatised naming (RAN) to word recognition may depend on the phonological regularity of the orthography. This study examined differential contributions of RAN to reading and writing in Korean alphabetic Hangul, logographic Hanja (Chinese) and English as a second language among 73 fifth graders in Korea across 1?year. RAN…

  17. Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results.

    PubMed

    Fernandez, Hubert H; Standaert, David G; Hauser, Robert A; Lang, Anthony E; Fung, Victor S C; Klostermann, Fabian; Lew, Mark F; Odin, Per; Steiger, Malcolm; Yakupov, Eduard Z; Chouinard, Sylvain; Suchowersky, Oksana; Dubow, Jordan; Hall, Coleen M; Chatamra, Krai; Robieson, Weining Z; Benesh, Janet A; Espay, Alberto J

    2015-04-01

    Motor complications in Parkinson's disease (PD) are associated with long-term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. L-dopa-carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG-J), which reduces L-dopa-plasma-level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54-week, open-label LCIG study. PD patients with severe motor fluctuations (>3 h/day "off" time) despite optimized therapy received LCIG monotherapy. Additional PD medications were allowed >28 days post-LCIG initiation. Safety was the primary endpoint measured through adverse events (AEs), device complications, and number of completers. Secondary endpoints included diary-assessed off time, "on" time with/without troublesome dyskinesia, UPDRS, and health-related quality-of-life (HRQoL) outcomes. Of 354 enrolled patients, 324 (91.5%) received PEG-J and 272 (76.8%) completed the study. Most AEs were mild/moderate and transient; complication of device insertion (34.9%) was the most common. Twenty-seven (7.6%) patients withdrew because of AEs. Serious AEs occurred in 105 (32.4%), most commonly complication of device insertion (6.5%). Mean daily off time decreased by 4.4 h/65.6% (P < 0.001). On time without troublesome dyskinesia increased by 4.8 h/62.9% (P < 0.001); on time with troublesome dyskinesia decreased by 0.4 h/22.5% (P = 0.023). Improvements persisted from week 4 through study completion. UPDRS and HRQoL outcomes were also improved throughout. In the advanced PD population, LCIG's safety profile consisted primarily of AEs associated with the device/procedure, l-dopa/carbidopa, and advanced PD. LCIG was generally well tolerated and demonstrated clinically significant improvements in motor function, daily activities, and HRQoL sustained over 54 weeks. PMID:25545465

  18. Foley Catheter for Induction of Labor at Term: An Open-Label, Randomized Controlled Trial

    PubMed Central

    Wang, Zhiqun; Dai, Yimin; Zheng, Mingming; Xu, Biyun; Hu, Yali

    2015-01-01

    Objective This study aimed to determine the optimal Foley catheter balloon volume (30-mL vs. 80-mL) and the maximum time for cervical ripening (12 hours vs. 24 hours) to improve vaginal delivery rate within 24 hours of induction. Methods We conducted an open-label, randomized controlled trial in a teaching hospital in China. Women with a term singleton pregnancy, cephalic presentation, intact membrane and an unfavorable cervix (Bishop score <6) were randomly allocated, in 1:1:1:1 ratio, to receive either one of the four treatments: (1) 30-mL balloon for a maximum of 12 hours, (2) 30-mL balloon for a maximum of 24 hours, (3) 80-mL balloon for a maximum of 12 hours, and (4) 80-mL balloon for a maximum of 24 hours. The primary outcome was vaginal delivery within 24 hours. Secondary outcomes included cesarean section rate and maternal/neonatal morbidity. Data were analyzed on a per-protocol basis. Results Five hundred and four women were recruited and randomized (126 women in each group); nine women did not receive the assigned intervention. More women achieved vaginal delivery within 24 hours in 12-hour Foley catheter groups than in the 24-hour Foley catheter groups (30-mL/12 hours: 54.5%, 30-mL/24 hours: 33.1%, 80-mL/12 hours: 46.4%, 80-mL/24 hours: 24.0%, p < 0.001). Cesarean section rates and the incidence of chorioaminonitis were comparable among four groups. After adjustment for confounding factors, both ripening time and balloon size did not affect the proportion of women delivered vaginally within 24 hours of induction. Conclusion For women with an unfavorable cervix at term, induction of labor with a Foley catheter is safe and effective. Higher balloon volume (80-mL vs. 30-mL) and longer ripening time (24 hours vs. 12 hours) would not shorten induction to delivery interval or reduce cesarean section rate. Trial Registration Chinese Clinical trial registry (ChiCTR-TRC-13003044) PMID:26322635

  19. Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial

    PubMed Central

    Aubin, H-J; Bobak, A; Britton, J R; Oncken, C; Billing, C B; Gong, J; Williams, K E; Reeves, K R

    2008-01-01

    Background: Varenicline, a new treatment for smoking cessation, has demonstrated significantly greater efficacy over placebo and sustained release bupropion (bupropion SR). A study was undertaken to compare a 12-week standard regimen of varenicline with a 10-week standard regimen of transdermal nicotine replacement therapy (NRT) for smoking cessation. Methods: In this 52-week, open-label, randomised, multicentre, phase 3 trial conducted in Belgium, France, the Netherlands, UK and USA, participants were randomly assigned (1:1) to receive varenicline uptitrated to 1 mg twice daily for 12 weeks or transdermal NRT (21 mg/day reducing to 7 mg/day) for 10 weeks. Non-treatment follow-up continued to week 52. The primary outcome was the biochemically confirmed (exhaled carbon monoxide ⩽10 ppm) self-reported continuous abstinence rate (CAR) for the last 4 weeks of the treatment period in participants who had taken at least one dose of treatment. Secondary outcomes included CAR from the last 4 weeks of treatment through weeks 24 and 52, and measures of craving, withdrawal and smoking satisfaction. Results: A total of 376 and 370 participants assigned to varenicline and NRT, respectively, were eligible for analysis. The CAR for the last 4 weeks of treatment was significantly greater for varenicline (55.9%) than NRT (43.2%; OR 1.70, 95% CI 1.26 to 2.28, p<0.001). The week 52 CAR (NRT, weeks 8–52; varenicline, weeks 9–52) was 26.1% for varenicline and 20.3% for NRT (OR 1.40, 95% CI 0.99 to 1.99, p = 0.056). Varenicline significantly reduced craving (p<0.001), withdrawal symptoms (p<0.001) and smoking satisfaction (p<0.001) compared with NRT. The most frequent adverse event was nausea (varenicline, 37.2%; NRT, 9.7%). Conclusions: The outcomes of this trial established that abstinence from smoking was greater and craving, withdrawal symptoms and smoking satisfaction were less at the end of treatment with varenicline than with transdermal NRT. Trial registration number

  20. After the diabetes care trial ends, now what? A 1-year follow-up of the RxING study

    PubMed Central

    Al Hamarneh, Yazid N; Sauriol, Luc; Tsuyuki, Ross T

    2015-01-01

    Introduction There is strong evidence that pharmacist care improves patients’ glycaemic control. However, the sustainability and durability of such interventions beyond the research period is not known. RxING was the first trial of pharmacist prescribing in diabetes and it showed an improvement in glycated haemoglobin (HbA1c) of 1.8% over 6 months. Objective 1° objective: To evaluate glycaemic control in the RxING study patients 12 months after the end of the formal study follow-up. 2° objective: To assess the patients’ risk of cardiovascular events in the next 10 years. Methods We contacted the participating pharmacists to check if the patients who participated in the RxING study are still taking insulin, the dose of insulin they are taking, and their HbA1c. There were no mandated follow-up visits with the pharmacist after the study completion. Results A total of 100 patients with poorly controlled type 2 diabetes were enrolled in the original RxING study; 93 of them completed the study, while 83 participated in the 12-month follow-up. Seventy-five patients were still taking insulin, with the average dose increasing from 31.1 units (SD 18.4) at study completion to 37.4 units (SD 30.8) (95% CI −13.3 to 0.88, p=0.085). HbA1c was reduced from 9.1% (SD 1) at baseline to 7.3% (SD 0.9) at study completion (95% CI 1.4 to 2, p <0.001), and increased to 8.1% (SD 1.3) 12 months later (95% CI −1.1 to −0.5, p <0.001 vs study completion). Conclusions Twelve months after completing the intervention, approximately half of the glycaemic control gains were lost. This highlights the importance of structured follow-up with the pharmacist in this patient population. Trial registration number clinicaltrials.gov; Identifier: NCT01335763. PMID:26270946

  1. Evaluation of the Mandibular Function, after Nonsurgical Treatment of Unilateral Subcondylar Fracture: A 1-Year Follow-Up Study.

    PubMed

    K M, Sudheesh; Desai, Rajendra; K Sn, Siva Bharani; S, Subhalakshmi

    2016-09-01

    There are no clearly defined guidelines for when an open or closed treatment is indicated for treatment of mandibular condylar fractures. The aim of the study is to analyze the mandibular function after nonsurgical treatment of unilateral subcondylar fractures, in a prospective study. A prospective study was conducted on 30 patients with unilateral mandibular subcondylar fracture undergoing nonsurgical treatment. Clinical and radiographic examinations were done prior to treatment and at 12-month follow-up. Pain, perceived occlusion, mouth opening, protrusion, and horizontal movements of the mandible were evaluated by clinical examination. Radiologic evaluation was done using Panoramic and Reverse Towne's radiographs. At 12-month follow-up, there was minimal pain in the temporomandibular joint region, there was an improvement in the perceived occlusion, and mouth opening did not reduce. There was insignificant absolute difference between left and right lateral mandibular movements. The amount of increase in the protrusion of mandible was insignificant. On radiographic evaluation, the degree of coronal and sagittal displacement was insignificant at follow-up. Mean ramus height pretreatment and 12 months posttreatment were 0.98 ± 0.50 and 0.87 ± 0.47, respectively. Based on this study, patients had adequate mandibular function and minimal pain after nonsurgical treatment. Unilateral subcondylar fractures of the mandible can be treated nonsurgically in patients with minimal occlusal discrepancies, adequate mouth opening, minimal displacement of condyle, and minimal ramus height shortening. PMID:27516838

  2. Morbid obese adults increased their sense of coherence 1 year after a patient education course: a longitudinal study

    PubMed Central

    Fagermoen, May Solveig; Hamilton, Glenys; Lerdal, Anners

    2015-01-01

    Background Personal factors are key elements to understand peoples’ health behavior. Studies of such factors are important to develop targeted interventions to improve health. The main purpose of this study is to explore sense of coherence (SOC) in a sample of persons with morbid obesity before and after attending a patient education course and to explore the association between SOC and sociodemographic and other personal factors. Methods In this longitudinal purposely sampled study, the participants completed questionnaires on the first day of the course and 12 months after course completion. Sixty-eight participants had valid scores on the selected variables at follow-up: SOC, self-esteem, and self-efficacy. Relationships were assessed with correlation analyses and paired and independent samples t-tests and predictors with linear regression analyses. Results From baseline to follow-up, the total SOC score and the subdimension scores comprehensibility, manageability, and meaningfulness all increased significantly. At both time points, the SOC scores were low compared to the general population but similar to scores in other chronically ill. At baseline, a multivariate analysis showed that older age, having paid work, and higher self-esteem were directly related to higher total SOC score after controlling for other sociodemographic factors and the participants’ level of self-efficacy. Multivariate analyses of the relationship between baseline predictors of SOC at 12-month follow-up, controlling for baseline SOC scores or sociodemographic or personal factors, revealed that none of these variables independently predicted SOC scores at follow-up. Conclusion The total SOC score and its subdimensions increased significantly at follow-up. SOC may be a useful outcome measure for lifestyle interventions in people with morbid obesity and possibly other health care problems. Subdimension scores may give an indication of what is poorly developed and needs strengthening

  3. Religious Affiliation as a Predictor of Involuntary Psychiatric Admission: A Brazilian 1-Year Follow-Up Study

    PubMed Central

    Casella, Caio Borba; Loch, Alexandre Andradade

    2014-01-01

    Objective: The aim of this study was to analyze factors associated with the legal status at psychiatric admission of individuals with psychosis or bipolar disorder in a Latin-American cultural setting. Methods: Prospective observational study was conducted in São Paulo, Brazil. We analyzed 169 individuals with bipolar or psychotic disorder in need of hospitalization. Sociodemographic data, data on the psychiatric disorder, information about the hospital stay, and data at time of discharge were collected. Their families were also contacted by telephone and interviews were conducted at 1, 2, 6, and 12 months post-discharge as a follow-up. Results: Eighty-eight patients (52%) had a voluntary admission and 81 (48%) had an involuntary admission (IA). The average length of admission was similar in both groups (17.4 vs. 17.3 days, p = 0.22). It was significantly more common for IA patients to be admitted because of other-directed aggressiveness (47.7 vs. 65.4%, p = 0.02). The percentage of individuals that needed physical restraint during hospital stay among IA patients was also significantly higher (11.4 vs. 25.9%, p = 0.01). Having any religious affiliations was significantly related to an IA status as well (OR = 4–6.48). Conclusion: Our results suggest that cultural factors related to religious affiliations might play an important role in determining psychiatric hospitalization legal status. Religion might possibly influence someone’s judgment and insight about his/her psychiatric disorder. This study restates the importance of dealing with the subject of religion with patients. PMID:25157344

  4. Bone mineral density of the proximal femur after hip resurfacing arthroplasty: 1-year follow-up study

    PubMed Central

    2011-01-01

    Background Hip resurfacing arthroplasty (HRA) is considered a bone-preserving procedure and may eliminate proximal femoral stress shielding and osteolysis. However, in addition to implant-related stress-shielding factors, various patient-related factors may also have an effect on bone mineral density (BMD) of the proximal femur in patients with HRA. Thus, we studied the effects of stem-neck angle, demographic variables, and physical functioning on the BMD of the proximal femur in a one-year follow-up. Methods Thirty three patients (9 females and 24 males) with a mean (SD) age of 55 (9) years were included in the study. BMD was measured two days and 3, 6, and 12 months postoperatively and 10 regions of interest (ROI) were used. Stem-neck angle was analyzed from anteroposterior radiographs. Results Three months postoperatively, BMD decreased in six out of 10 regions of interest (ROI) on the side operated on and in one ROI on the control side (p < 0.05) compared to the second postoperative day. At 12 months, BMD had increased in 7 ROIs on the operated side and one ROI on the control side (all p < 0.001). Correlation was found between the stem-neck angle and BMD in ROIs 2, 3, 7, and 9 (r = 0.36 - 0.61). In multiple regression analysis, stem-neck angle, age, sex, body mass index, and walking distance did not explain the BMD changes. Conclusions After an early drop, the BMD of the upper femur was restored and even exceeded the preoperative level at one year follow-up. From a clinical standpoint, the changes in BMD in these HRA patients could not be explained by stem-neck angle or patient related factors. PMID:21595913

  5. Effects of phytoestrogen genistein on cytogenetic biomarkers in postmenopausal women: 1 year randomized, placebo-controlled study.

    PubMed

    Atteritano, Marco; Pernice, Francesco; Mazzaferro, Susanna; Mantuano, Stefania; Frisina, Alessia; D'Anna, Rosario; Cannata, Maria Letizia; Bitto, Alessandra; Squadrito, Francesco; Frisina, Nicola; Buemi, Michele

    2008-07-28

    To evaluate in a twelve-month, randomized placebo-controlled study whether pure administration of phytoestrogen genistein (54 mg/day) might reduce cytogenetic biomarkers in peripheral lymphocytes of postmenopausal women. A total of 57 postmenopausal women met the criteria and were randomly assigned to receive phytoestrogen genistein (n = 30) or placebo (n = 27). There was no significant difference in age, length of time since menopause or body mass index between the two groups. After one year, plasma genistein level was 0.14 +/- 0.01 micromol/L in the control group and 0.72 +/- 0.08 micromol/L in the genistein group (P < 0.0001). At baseline, sister chromatid exchange rate was 4.97 +/- 2.17 in the control group and 4.96 +/- 1.83 in the genistein group (P = 0.89). After one year, sister chromatid exchange rate was 4.96 +/- 2.16 in the control group and 3.98 +/- 1.14 in the genistein group (P < 0.05). High frequency cells count was 3% in the genistein group and 5% in the control group (P < 0.05) at the end of the study. Chromosomal aberration frequency was 5.55% in the control group at time 0 and 5.75% in the genistein group; after one year, the figures were 5.86% in the control group and 4.5% in the genistein group (P < 0.05). After one year, there was a negative relationship between sister chromatid exchange rate and plasma levels (r = - 0.43; P < 0.05) in the genistein group. Phytoestrogen genistein has been shown in postmenopausal women to be effective in the reduction of cytogenetic biomarkers. The protective effect on genomic damage appears to be a particularly promising tool in reducing the risk of cancer.

  6. Psychological and Work Stress Assessment of Patients following Angioplasty or Heart Surgery: Results of 1-year Follow-up Study.

    PubMed

    Fiabane, Elena; Giorgi, Ines; Candura, Stefano M; Argentero, Piergiorgio

    2015-12-01

    The aim of this study was to explore changes in subjective psychological health and perceived work stress among patients who returned to work (RTW) after a multidisciplinary cardiac rehabilitation (CR) following cardiac interventions. A total of 108 patients were evaluated at the beginning of their CR, at 6 and 12 months after discharge. Self-report questionnaires were used to assess depression, anxiety, illness perception and work stress at each time stage. Results showed reports of depressive symptoms significantly decreased (p < 0.05) and subjective mental (p = 0.001) and physical health (p < 0.001) improved over time. Patients revealed a decrease in Type A behaviour pattern (p < 0.001) and in job satisfaction levels (p = 0.01), greater internal locus of control (p < 0.01) and increased use of the coping strategy 'Involvement' (p < 0.01). Major findings are that cardiac patients had an improvement in subjective psychological health and did not perceive increased work stress after their RTW. Patients' psychological health and work stress need to be assessed during the CR and should be also carefully monitored after the RTW in order to identify patients' psychological and work-related barriers and facilitate a safe and successful work reintegration.

  7. Daily-Life Gait Quality as Predictor of Falls in Older People: A 1-Year Prospective Cohort Study

    PubMed Central

    van Schooten, Kimberley S.; Pijnappels, Mirjam; Rispens, Sietse M.; Elders, Petra J. M.; Lips, Paul; Daffertshofer, Andreas; Beek, Peter J.; van Dieën, Jaap H.

    2016-01-01

    Falls can have devastating consequences for older people. We determined the relationship between the likelihood of fall incidents and daily-life behavior. We used wearable sensors to assess habitual physical activity and daily-life gait quality (in terms of e.g. stability, variability, smoothness and symmetry), and determined their predictive ability for time-to-first-and-second-falls. 319 older people wore a trunk accelerometer (Dynaport MoveMonitor, McRoberts) during one week. Participants further completed questionnaires and performed grip strength and trail making tests to identify risk factors for falls. Their prospective fall incidence was followed up for six to twelve months. We determined interrelations between commonly used gait characteristics to gain insight in their interpretation and determined their association with time-to-falls. For all data -including questionnaires and tests- we determined the corresponding principal components and studied their predictive ability for falls. We showed that gait characteristics of walking speed, stride length, stride frequency, intensity, variability, smoothness, symmetry and complexity were often moderately to highly correlated (r > 0.4). We further showed that these characteristics were predictive of falls. Principal components dominated by history of falls, alcohol consumption, gait quality and muscle strength proved predictive for time-to-fall. The cross-validated prediction models had adequate to high accuracy (time dependent AUC of 0.66–0.72 for time-to-first-fall and 0.69–0.76 for -second-fall). Daily-life gait quality obtained from a single accelerometer on the trunk is predictive for falls. These findings confirm that ambulant measurements of daily behavior contribute substantially to the identification of elderly at (high) risk of falling. PMID:27389583

  8. Daily-Life Gait Quality as Predictor of Falls in Older People: A 1-Year Prospective Cohort Study.

    PubMed

    van Schooten, Kimberley S; Pijnappels, Mirjam; Rispens, Sietse M; Elders, Petra J M; Lips, Paul; Daffertshofer, Andreas; Beek, Peter J; van Dieën, Jaap H

    2016-01-01

    Falls can have devastating consequences for older people. We determined the relationship between the likelihood of fall incidents and daily-life behavior. We used wearable sensors to assess habitual physical activity and daily-life gait quality (in terms of e.g. stability, variability, smoothness and symmetry), and determined their predictive ability for time-to-first-and-second-falls. 319 older people wore a trunk accelerometer (Dynaport MoveMonitor, McRoberts) during one week. Participants further completed questionnaires and performed grip strength and trail making tests to identify risk factors for falls. Their prospective fall incidence was followed up for six to twelve months. We determined interrelations between commonly used gait characteristics to gain insight in their interpretation and determined their association with time-to-falls. For all data -including questionnaires and tests- we determined the corresponding principal components and studied their predictive ability for falls. We showed that gait characteristics of walking speed, stride length, stride frequency, intensity, variability, smoothness, symmetry and complexity were often moderately to highly correlated (r > 0.4). We further showed that these characteristics were predictive of falls. Principal components dominated by history of falls, alcohol consumption, gait quality and muscle strength proved predictive for time-to-fall. The cross-validated prediction models had adequate to high accuracy (time dependent AUC of 0.66-0.72 for time-to-first-fall and 0.69-0.76 for -second-fall). Daily-life gait quality obtained from a single accelerometer on the trunk is predictive for falls. These findings confirm that ambulant measurements of daily behavior contribute substantially to the identification of elderly at (high) risk of falling. PMID:27389583

  9. Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial

    PubMed Central

    Rossi, Roberta; Bonanni, Alice; Quinn, Robert R.; Sica, Felice; Bodria, Monica; Pasini, Andrea; Montini, Giovanni; Edefonti, Alberto; Belingheri, Mirco; De Giovanni, Donatella; Barbano, Giancarlo; Degl’Innocenti, Ludovica; Scolari, Francesco; Murer, Luisa; Reiser, Jochen; Fornoni, Alessia; Ghiggeri, Gian Marco

    2015-01-01

    Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1–16 years who had developed SDNS in the previous 6–12 months and were maintained in remission with high prednisone doses (≥0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m2; intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6–13.5 years]) were enrolled and followed for ≤60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS. PMID:25592855

  10. Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder.

    PubMed

    Husted, David S; Shapira, Nathan A; Murphy, Tanya K; Mann, Giselle D; Ward, Herbert E; Goodman, Wayne K

    2007-01-01

    Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

  11. Transient hypogammaglobulinemia and severe atopic dermatitis: Open-label treatment with immunoglobulin in a case series

    PubMed Central

    Lin, Joanna H.; Roberts, Robert; Lim, Kellie J.; Stiehm, E. Richard

    2016-01-01

    Background: We reported on six infants between 5 and 11 months old, with transient hypogammaglobulinemia of infancy and severe refractory atopic dermatitis, who were treated with open-label immunoglobulin (Ig) after conventional therapy failed. All six infants had an IgG level of <225 mg/dL, elevated eosinophil and IgE levels, and no urine or stool protein losses, but they did exhibit hypoalbuminemia. Objective: To evaluate the utility of open-label immunoglobulin in infants with severe atopic dermatitis for whom conventional therapy failed. We reviewed the clinical utility of intravenous immunoglobulin in the treatment of severe atopic dermatitis, the most recent research in the field, and suggested mechanisms for its benefit. Methods: The six infants were identified from a retrospective chart review at the University of California Los Angeles Allergy and Immunology outpatient pediatric clinic. Results: All six patients were treated with 400 mg/kg/month of intravenous immunoglobulin and had normalization of their IgG and albumin levels, and all but one had clinically improved atopic dermatitis. Conclusion: Infants with severe atopic dermatitis who did not respond to conventional therapy avoidance may benefit from intravenous immunoglobulin therapy. PMID:27470901

  12. Short- and Long-Term Efficacy of Intensive Rehabilitation Treatment on Balance and Gait in Parkinsonian Patients: A Preliminary Study with a 1-Year Followup

    PubMed Central

    Bertotti, Gabriella; Uccellini, Davide; Boveri, Natalia; Rovescala, R.; Pezzoli, Gianni

    2013-01-01

    Parkinson's disease (PD) is a neurodegenerative disease in which gait and balance disturbances are relevant symptoms that respond poorly to pharmacological treatment. The aim of this study was to investigate whether a 4-week inpatient multidisciplinary intensive rehabilitation treatment (MIRT) is effective in improving balance and gait and whether improvements persist at a one-year followup. We studied 20 PD inpatients (stage 3 Hoehn-Yahr) who underwent a MIRT. Outcome measures were UPDRS items for balance (30), falls (13), and walk (29), Berg Balance Scale, six-minute walking test, Timed Up and Go Test, and Comfortable-Fast gait speeds. Patients were evaluated at admission, at the end of the 4-week treatment, and at a 1-year followup. Pharmacological therapy was unchanged during MIRT and follow-up. All outcome measures improved significantly at the end of treatment. At 1-year follow-up control, UPDRS walk and Comfortable-Fast gait speeds still maintained better values with respect to admission (P = 0.009, P = 0.03, and P = 0.02, resp.), while the remaining scales did not differ significantly. Our results demonstrate that the MIRT was effective in improving balance and gait and that the improvement in gait performances was partially maintained also after 1 year. PMID:23766927

  13. Hospitalization for Pneumonia is Associated With Decreased 1-Year Survival in Patients With Type 2 Diabetes: Results From a Prospective Cohort Study.

    PubMed

    Falcone, Marco; Tiseo, Giusy; Russo, Alessandro; Giordo, Laura; Manzini, Elisa; Bertazzoni, Giuliano; Palange, Paolo; Taliani, Gloria; Cangemi, Roberto; Farcomeni, Alessio; Vullo, Vincenzo; Violi, Francesco; Venditti, Mario

    2016-02-01

    Diabetes mellitus is a frequent comorbid conditions among patients with pneumonia living in the community.The aim of our study is to evaluate the impact of hospitalization for pneumonia on early (30 day) and late mortality (1 year) in patients with type 2 diabetes mellitus.Prospective comparative cohort study of 203 patients with type 2 diabetes hospitalized for pneumonia versus 206 patients with diabetes hospitalized for other noninfectious causes from January 2012 to December 2013 at Policlinico Umberto I (Rome). Enrolled patients were followed up to discharge and up to 1 year after initial hospital admission or death.Overall, 203 patients with type 2 diabetes admitted to hospital for pneumonia were compared to 206 patients with type 2 diabetes admitted for other causes (39.3% decompensated diabetes, 21.4% cerebrovascular diseases, 9.2% renal failure, 8.3% acute myocardial infarction, and 21.8% other causes). Compared to control patients, those admitted for pneumonia showed a higher 30-day (10.8% vs 1%, P < 0.001) and 1-year mortality rate (30.3% vs 16.8%, P < 0.001). Compared to survivors, nonsurvivor patients with pneumonia had a higher incidence of moderate to severe chronic kidney disease, hemodialysis, and malnutrition were more likely to present with a mental status deterioration, and had a higher number of cardiovascular events during the follow-up period. Cox regression analysis found age, Charlson comorbidity index, pH < 7.35 at admission, hemodialysis, and hospitalization for pneumonia as variables independently associated with mortality.Hospitalization for pneumonia is associated with decreased 1-year survival in patients with type 2 diabetes, and appears to be a major determinant of long-term outcome in these patients.

  14. Free thyroxine levels are associated with cognitive changes in individuals with a first episode of psychosis: A prospective 1-year follow-up study.

    PubMed

    Labad, J; Barbero, J D; Gutiérrez-Zotes, A; Montalvo, I; Creus, M; Cabezas, Á; Solé, M; Algora, M J; Garcia-Parés, G; Vilella, E

    2016-03-01

    The results of previous cross-sectional studies suggest that free thyroxine (FT4) levels are associated with cognitive abilities (particularly attention/vigilance) during the early stages of psychosis. We aimed to explore whether hypothalamic-pituitary-thyroid hormones predict cognitive changes in a 1-year longitudinal study following first episodes of psychosis (FEP). We studied 36 FEP patients and a control group of 50 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH) and FT4 were measured. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery (MCCB). FEP patients were assessed twice (baseline and after 1year), whereas HS were assessed only once. We compared cognitive changes at 1year between three groups based on baseline FT4 levels: 1) lowest quartile (Q1, FT4<1.16ng/dL); 2) medium quartiles (Q2-Q3, FT4 1.16-1.54ng/dL); and 3) highest quartile (Q4, FT4>1.54ng/dL). No differences in TSH or FT4 levels were found between HS and FEP patients. All participants had FT4 levels within the normal range. HS outperformed FEP patients in all cognitive tasks. In relation to the relationship between FT4 levels and cognitive changes, a U-shaped pattern was observed: FEP patients from the middle quartiles (Q2-Q3) improved in attention/vigilance, whereas both extreme quartiles (Q1 and Q4) showed a worsening in this cognitive domain over time. Patients with lower FT4 (Q1) showed poorer baseline attention; therefore, lower baseline FT4 levels predicted a poorer prognosis in terms of attention performance. Our study suggests that baseline FT4 levels are associated with changes in attention and vigilance performance over one year in FEP patients. PMID:26805411

  15. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

    PubMed

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-01-01

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism. PMID:27338456

  16. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

    PubMed

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-06-07

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  17. Effects of Shenfu Injection in the Treatment of Septic Shock Patients: A Multicenter, Controlled, Randomized, Open-Label Trial

    PubMed Central

    Zhang, Xinchao; Lin, Peihong; Wei, Jie; Cao, Yu; Pan, Shuming; Walline, Joseph; Qian, Chuanyun; Shan, Zhigang

    2016-01-01

    The effect of Shenfu on biochemical parameters and survival during resuscitation in patients with septic shock was examined. This was a multicenter, controlled, randomized, open-label trial carried out in 210 patients with septic shock from seven medical centers in China. They were randomized to Shenfu or saline. The primary outcome was lactate clearance. The secondary outcomes were shock index normalization, dose of vasopressors, ICU stay, hospital stay, and mortality. A total of 199 patients completed the trial. Blood pressure, heart rate, and other routine lab tests showed no difference between the groups. Lactate levels and lactate clearance were similar between the two groups. Hospital and ICU stay were similar between the two groups. When considering all patients, the 7- and 28-day mortality were similar between the two groups, but when considering only patients with lactate levels ≥4.5 mmol/L, the Shenfu group showed a better 7-day survival than the control group (7 days: 83.3% versus 54.5%, P = 0.034; 28 days: 72.7% versus 47.6%, P = 0.092). Shenfu may improve the 7-day survival in patients with impaired lactate clearance (≥4.5 mmol/L), but the mechanism for this effect is unclear. Additional studies are necessary to characterize the hemodynamic changes after Shenfu infusion. This trial is registered with ChiCTR-TRC-11001369. PMID:27446222

  18. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

    PubMed Central

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-01-01

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism. PMID:27338456

  19. Negative Effects of Total Gastrectomy on Bone Tissue Metabolism and Volumetric Bone Mineral Density (vBMD) of Lumbar Spine in 1-Year Study in Men

    PubMed Central

    Krupski, Witold; Tatara, Marcin R.; Bury, Pawel; Szabelska, Anna; Charuta, Anna; Maciejewski, Ryszard; Wallner, Grzegorz; Dabrowski, Andrzej

    2016-01-01

    Abstract Gastrectomy induces severe osteoporosis in humans but its quantitative scale within trabecular and cortical compartments was not estimated. The aim of the study was to determine changes of volumetric bone mineral density (vBMD) in lumbar vertebrae (L1–L4) and biochemical bone metabolism markers in serum of patients 1 year after total gastrectomy. The control group consisted of patients (N = 8) subjected to abdominal surgery due to cardiospasmus. Total gastrectomy was performed in the experimental group (N = 6). Volumetric bone mineral density of trabecular and cortical bone of lumbar spine was measured before (baseline) and 1 year after the gastric surgery using the quantitative computed tomography method. Serum concentrations of insulin, insulin-like growth factor-1, tyroxine, interleukin-6, C-terminal telopeptides of type II collagen and bone formation, and resorption markers were determined at baseline and 1 year later, using ELISA, EIA, and IEMA methods. Total gastrectomy induced significant decrease of vBMD values, up to 16.8% and 10.0%, within the trabecular and cortical bone compartments of lumbar spine (P < 0.05). These negative changes of vBMD were associated with significantly increased serum concentration of bone resorption markers such as deoxypyridinoline, pyridinoline, and C-terminal telopeptides of type I collagen, by 13.5%, 32.2%, and 121.5%, respectively (P < 0.05). Neither vBMD nor biochemical bone turnover markers and hormone concentrations were influenced in the control patients. Dramatic bone loss during the first year in gastrectomized patients has proven dynamic osteoporosis progress indicating an importance of treatment interventions in these patients with emphasis on inhibition of intensive bone resorption processes. PMID:26886633

  20. The Development of Musical Skills of Underprivileged Children Over the Course of 1 Year: A Study in the Context of an El Sistema-Inspired Program.

    PubMed

    Ilari, Beatriz S; Keller, Patrick; Damasio, Hanna; Habibi, Assal

    2016-01-01

    Developmental research in music has typically centered on the study of single musical skills (e.g., singing, listening) and has been conducted with middle class children who learn music in schools and conservatories. Information on the musical development of children from different social strata, who are enrolled in community-based music programs, remains elusive. This study examined the development of musical skills in underprivileged children who were attending an El Sistema-inspired program in Los Angeles. We investigated how children, predominantly of Latino ethnicity, developed musically with respect to the following musical skills - pitch and rhythmic discrimination, pitch matching, singing a song from memory, and rhythmic entrainment - over the course of 1 year. Results suggested that participation in an El Sistema-inspired program affects children's musical development in distinct ways; with pitch perception and production skills developing faster than rhythmic skills. Furthermore, children from the same ethnic and social background, who did not participate in the El Sistema-inspired music program, showed a decline in singing and pitch discrimination skills over the course of 1 year. Taken together, these results are consistent with the idea of musical development as a complex, spiraling and recursive process that is influenced by several factors including type of musical training. Implications for future research are outlined.

  1. The Development of Musical Skills of Underprivileged Children Over the Course of 1 Year: A Study in the Context of an El Sistema-Inspired Program.

    PubMed

    Ilari, Beatriz S; Keller, Patrick; Damasio, Hanna; Habibi, Assal

    2016-01-01

    Developmental research in music has typically centered on the study of single musical skills (e.g., singing, listening) and has been conducted with middle class children who learn music in schools and conservatories. Information on the musical development of children from different social strata, who are enrolled in community-based music programs, remains elusive. This study examined the development of musical skills in underprivileged children who were attending an El Sistema-inspired program in Los Angeles. We investigated how children, predominantly of Latino ethnicity, developed musically with respect to the following musical skills - pitch and rhythmic discrimination, pitch matching, singing a song from memory, and rhythmic entrainment - over the course of 1 year. Results suggested that participation in an El Sistema-inspired program affects children's musical development in distinct ways; with pitch perception and production skills developing faster than rhythmic skills. Furthermore, children from the same ethnic and social background, who did not participate in the El Sistema-inspired music program, showed a decline in singing and pitch discrimination skills over the course of 1 year. Taken together, these results are consistent with the idea of musical development as a complex, spiraling and recursive process that is influenced by several factors including type of musical training. Implications for future research are outlined. PMID:26869964

  2. The Development of Musical Skills of Underprivileged Children Over the Course of 1 Year: A Study in the Context of an El Sistema-Inspired Program

    PubMed Central

    Ilari, Beatriz S.; Keller, Patrick; Damasio, Hanna; Habibi, Assal

    2016-01-01

    Developmental research in music has typically centered on the study of single musical skills (e.g., singing, listening) and has been conducted with middle class children who learn music in schools and conservatories. Information on the musical development of children from different social strata, who are enrolled in community-based music programs, remains elusive. This study examined the development of musical skills in underprivileged children who were attending an El Sistema-inspired program in Los Angeles. We investigated how children, predominantly of Latino ethnicity, developed musically with respect to the following musical skills – pitch and rhythmic discrimination, pitch matching, singing a song from memory, and rhythmic entrainment – over the course of 1 year. Results suggested that participation in an El Sistema-inspired program affects children’s musical development in distinct ways; with pitch perception and production skills developing faster than rhythmic skills. Furthermore, children from the same ethnic and social background, who did not participate in the El Sistema-inspired music program, showed a decline in singing and pitch discrimination skills over the course of 1 year. Taken together, these results are consistent with the idea of musical development as a complex, spiraling and recursive process that is influenced by several factors including type of musical training. Implications for future research are outlined. PMID:26869964

  3. A descriptive study on complementary and alternative medicine use in 0 to 1-year-old infants and nurses' awareness and recommendation for complementary and alternative medicine.

    PubMed

    Çalişkan, Nurcan; Yıldırım, Nuriye; Atalay, Sitem; Kavaklı, Müjde; Özdoğan, Ayşegül

    2015-10-01

    This study aimed to determine complementary and alternative medicine (CAM) recommended by midwives and nurses and used by mothers on their 0 to 1-year-old infants. A cross-sectional survey design was used. The sample of the study consisted of 65 midwives and mothers of 349 infants registered at these health-care centres. The frequency of CAM use on a regular basis by mothers participating in the study on their infants was 24.6%, whereas the frequency of CAM use for a while was 41.3%. Of the mothers using CAM, 81.5-98.5% stated that the method they were employing was useful. The mothers used CAM on their infants, and the midwives and nurses recommended CAM use. However, the midwives and nurses themselves should be first trained to be able to inform individuals/mothers about CAM. Evidence-based studies on CAM are needed.

  4. Longitudinal Changes in Resting-State Cerebral Activity in Patients with First-Episode Schizophrenia: A 1-Year Follow-up Functional MR Imaging Study.

    PubMed

    Li, Fei; Lui, Su; Yao, Li; Hu, Junmei; Lv, Peilin; Huang, Xiaoqi; Mechelli, Andrea; Sweeney, John A; Gong, Qiyong

    2016-06-01

    Purpose To determine whether the brain functional abnormalities of drug-naive first-episode schizophrenia are reduced after 1 year of undergoing antipsychotic treatment and whether pretreatment resting-state functional magnetic resonance (MR) imaging parameters are associated with longitudinal changes in clinical symptoms. Materials and Methods This prospective study was approved by the local ethical committee, and written informed consent was obtained from all participants. Twenty antipsychotic-naive first-episode patients with schizophrenia and 16 healthy individuals were recruited and underwent resting-state functional MR imaging at baseline and again at 1-year follow-up, by which time significant clinical improvement was seen. The amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were analyzed with analysis of covariance. Results The amount of ALFF in the right inferior parietal lobule (IPL) and orbitofrontal cortex (OFC) and the amount of FC between the bilateral IPLs significantly increased over the follow-up period, and the amount of ALFF in the right occipital gyrus was reduced (P < .050, AlphaSim corrected [ http://afni.nimh.nih.gov/pub/dist/doc/manual/AlphaSim.pdf ]), returning toward normal levels. Furthermore, the degree of alteration in ALFF values in the right OFC (P = .037) and occipital gyrus (P = .002) at baseline was significantly correlated with the magnitude of the normalization in those regions at 1-year follow-up. In contrast, abnormalities of ALFF in the bilateral thalamus, ventral medial prefrontal cortex, precuneus, and right amygdala and of FC between the right OFC and the dorsal medial prefrontal cortex at baseline did not improve in patients at 1-year follow-up. Conclusion These findings show that some, but not all, neurophysiologic alterations that occur during the acute phase of schizophrenia are normalized in the context of clinical improvement and suggest therapeutic implications for

  5. Thermal Aging Study of a Dow Corning SE 1700 Porous Structure Made by Direct Ink Writing: 1-Year Results and Long-Term Predictions

    SciTech Connect

    Small, Ward; Pearson, Mark A.; Maiti, Amitesh; Metz, Thomas R.; Duoss, Eric B.; Wilson, Thomas S.

    2015-11-13

    Dow Corning SE 1700 (reinforced polydimethylsiloxane) porous structures were made by direct ink writing (DIW). The specimens (~50% porosity) were subjected to various compressive strains (15, 30, 45%) and temperatures (room temperature, 35, 50, 70°C) in a nitrogen atmosphere (active purge) for 1 year. Compression set and load retention of the aged specimens were measured periodically during the study. Compression set increased with strain and temperature. After 1 year, specimens aged at room temperature, 35, and 50°C showed ~10% compression set (relative to the applied compressive deflection), while those aged at 70°C showed 20-40%. Due to the increasing compression set, load retention decreased with temperature, ranging from ~90% at room temperature to ~60-80% at 70°C. Long-term compression set and load retention at room temperature were predicted by applying time-temperature superposition (TTS). The predictions show compression set relative to the compressive deflection will be ~10-15% with ~70-90% load retention after 50 years at 15-45% strain, suggesting the material will continue to be mechanically functional. Comparison of the results to previously acquired data for cellular (M97*, M9760, M9763) and RTV (S5370) silicone foams suggests that the SE 1700 DIW porous specimens are on par with, or outperform, the legacy foams.

  6. The effects of colestilan versus placebo and sevelamer in patients with CKD 5D and hyperphosphataemia: a 1-year prospective randomized study

    PubMed Central

    Locatelli, Francesco; Spasovski, Goce; Dimkovic, Nada; Wanner, Christoph; Dellanna, Frank; Pontoriero, Giuseppe

    2014-01-01

    Background This study compared the effects of short-term titrated colestilan (a novel non-absorbable, non-calcium, phosphate binder) with placebo, and evaluated the safety and efficacy of colestilan over 1 year compared with sevelamer, in patients with chronic kidney disease (CKD) 5D. Methods This prospective multicentre study comprised a 4-week phosphate binder washout period, a 16-week short-term, flexible-dose, treatment period (including a 4-week placebo-controlled withdrawal period) and a 40-week extension treatment phase. Results At Week 16 (the end of the 4-week placebo-controlled withdrawal period), serum phosphorus level was 0.43 mmol/L (1.32 mg/dL) lower with colestilan than placebo (P < 0.001; primary end point). Serum LDL-C level was also lower with colestilan than with placebo (P < 0.001). Both colestilan and sevelamer produced significant reductions from baseline in serum phosphorus levels (P < 0.001), maintained for 1 year, and the proportion of patients achieving target levels of ≤1.78 mmol/L (5.5 mg/dL) or ≤1.95 mmol/L (6.0 mg/dL) at study end were similar (65.3 and 73.3%, respectively, for colestilan, and 66.9 and 77.4%, respectively, for sevelamer). Serum calcium level remained stable in the colestilan group but tended to increase slightly in the sevelamer group (end-of-study increase of 0.035 mmol/L over baseline). Both binders produced similar reductions from baseline in LDL-C level (P < 0.001), and responder rates after 1 year, using a target of <1.83 mmol/L (70 mg/dL) or <2.59 mmol/L (100 mg/dL) were similar in both groups (50.7 and 85.3% for colestilan and 54.0 and 80.6% for sevelamer). Colestilan was generally well tolerated. Conclusions Colestilan is effective and safe for the treatment of hyperphosphataemia in patients with CKD 5D, and affords similar long-term phosphorus and cholesterol reductions/responder rates to sevelamer. PMID:24302608

  7. Is “Football for All” Safe for All? Cross-Sectional Study of Disparities as Determinants of 1-Year Injury Prevalence in Youth Football Programs

    PubMed Central

    Dahlström, Örjan; Backe, Stefan; Ekberg, Joakim; Janson, Staffan; Timpka, Toomas

    2012-01-01

    Background Football (soccer) is endorsed as a health-promoting physical activity worldwide. When football programs are introduced as part of general health promotion programs, equal access and limitation of pre-participation disparities with regard to injury risk are important. The aim of this study was to explore if disparity with regard to parents’ educational level, player body mass index (BMI), and self-reported health are determinants of football injury in community-based football programs, separately or in interaction with age or gender. Methodology/Principal Findings Four community football clubs with 1230 youth players agreed to participate in the cross-sectional study during the 2006 season. The study constructs (parents’ educational level, player BMI, and self-reported health) were operationalized into questionnaire items. The 1-year prevalence of football injury was defined as the primary outcome measure. Data were collected via a postal survey and analyzed using a series of hierarchical statistical computations investigating associations with the primary outcome measure and interactions between the study variables. The survey was returned by 827 (67.2%) youth players. The 1-year injury prevalence increased with age. For youths with parents with higher formal education, boys reported more injuries and girls reported fewer injuries than expected; for youths with lower educated parents there was a tendency towards the opposite pattern. Youths reporting injuries had higher standardized BMI compared with youths not reporting injuries. Children not reporting full health were slightly overrepresented among those reporting injuries and underrepresented for those reporting no injury. Conclusion Pre-participation disparities in terms of parents’ educational level, through interaction with gender, BMI, and self-reported general health are associated with increased injury risk in community-based youth football. When introduced as a general health promotion

  8. Perinatal Exposure to Traffic-Related Air Pollution and Atopy at 1 Year of Age in a Multi-Center Canadian Birth Cohort Study

    PubMed Central

    Allen, Ryan W.; Becker, Allan; Brook, Jeffrey R.; Mandhane, Piush; Scott, James A.; Sears, Malcolm R.; Subbarao, Padmaja; Takaro, Tim K.; Turvey, Stuart E.; Brauer, Michael

    2015-01-01

    Background The role of traffic-related air pollution (TRAP) exposure in the development of allergic sensitization in children is unclear, and few birth cohort studies have incorporated spatiotemporal exposure assessment. Objectives We aimed to examine the association between TRAP and atopy in 1-year-old children from an ongoing national birth cohort study in four Canadian cities. Methods We identified 2,477 children of approximately 1 year of age with assessment of atopy for inhalant (Alternaria, Der p, Der f, cat, dog, cockroach) and food-related (milk, eggs, peanuts, soy) allergens. Exposure to nitrogen dioxide (NO2) was estimated from city-specific land use regression models accounting for residential mobility and temporal variability in ambient concentrations. We used mixed models to examine associations between atopy and exposure during pregnancy and the first year of life, including adjustment for covariates (maternal atopy, socioeconomic status, pets, mold, nutrition). We also conducted analyses stratified by time-location patterns, daycare attendance, and modeled home ventilation. Results Following spatiotemporal adjustment, TRAP exposure after birth increased the risk for development of atopy to any allergens [adjusted odds ratio (aOR) per 10 μg/m3 NO2 = 1.16; 95% CI: 1.00, 1.41], but not during pregnancy (aOR = 1.02; 95% CI: 0.86, 1.22). This association was stronger among children not attending daycare (aOR = 1.61; 95% CI: 1.28, 2.01) compared with daycare attendees (aOR = 1.05; 95% CI: 0.81, 1.28). Trends to increased risk were also found for food (aOR = 1.17; 95% CI: 0.95, 1.47) and inhalant allergens (aOR = 1.28; 95% CI: 0.93, 1.76). Conclusion Using refined exposure estimates that incorporated temporal variability and residential mobility, we found that traffic-related air pollution during the first year of life was associated with atopy. Citation Sbihi H, Allen RW, Becker A, Brook JR, Mandhane P, Scott JA, Sears MR, Subbarao P, Takaro TK, Turvey SE

  9. Relation between initial treatment strategy in stable coronary artery disease and 1-year costs in Ontario: a population-based cohort study

    PubMed Central

    Kang, Jaskaran S.; Bennell, Maria C.; Qiu, Feng; Knudtson, Merril L.; Austin, Peter C.; Ko, Dennis T.; Wijeysundera, Harindra C.

    2016-01-01

    Background: Cardiovascular disease is costly, and annual expenditures are projected to increase. Our objective was to examine the variation in patient-level costs and identify drivers of cost in patients with stable coronary artery disease. Methods: In this retrospective cohort study using administrative databases in Ontario, Canada, we identified all patients with stable coronary artery disease after index angiography between Oct. 1, 2008, and Sept. 30, 2011. We excluded patients with a myocardial infarction within 90 days before the index, with normal coronaries, or with mild coronary disease. We categorized hospitals into low, medium or high revascularization ratio centres. The primary outcome was cumulative 1-year health care costs. A hierarchical generalized linear model identified patient, physician and hospital characteristics associated with patient costs, with 2 main covariates of interest: treatment allocation (medical v. percutaneous coronary intervention v. coronary artery bypass grafting) and hospital revascularization ratio. Results: A total of 183 630 angiography procedures were performed in Ontario during the study period. The final cohort included 39 126 patients with stable coronary artery disease, of which 15 138 received medical treatment and 23 988 received revascularization. The mean 1-year cost was $24 026 (interquartile range $8235-$30 511). The mean costs for medical management and revascularization were $18 069 and $27 786, respectively. The strongest predictor of costs was revascularization (percutaneous coronary intervention: cost ratio 1.27, 95% CI [confidence interval] 1.24-1.31; coronary artery bypass grafting: cost ratio 2.62, 95% CI 2.53-2.71). Hospital revascularization ratio did not significantly affect costs. There was no significant interaction between treatment and revascularization ratio. Interpretation: Most health care costs were due to acute care hospital admissions, and costs were higher for patients undergoing

  10. Marginal bone response of implants with platform switching and non-platform switching abutments in posterior healed sites: a 1-year prospective study

    PubMed Central

    Wang, Yun-Chi; Kan, Joseph Y K; Rungcharassaeng, Kitichai; Roe, Phillip; Lozada, Jaime L

    2015-01-01

    Objectives This 1-year prospective study evaluated the implant success rate and marginal bone response of non-submerged implants with platform and non-platform switching abutments in posterior healed sites. Material and methods Nineteen patients (9 male, 10 female) with posterior partially edentulous spaces, between the ages of 23 and 76 (mean = 55.4 years), were included in this study. A total of 30 implants (15 implants restored with platform switching [PS] abutments [control] and 15 implants restored with non-platform switching [NPS] abutments [test]) were assigned between two groups using a randomization procedure. The definitive abutments with conical connections were placed at the time of surgery, and the definitive restorations were placed at 3 months. All patients were evaluated clinically and radiographically using standardized radiographs at time of implant placement (0), 3, 6 and 12 months after implant placement. Data were analyzed using Friedman test with post hoc pairwise comparisons, Mann–Whitney U-test, and Pearson's chi-square test at the significance level of α = 0.05. Results At 12 months, all 30 implants remained osseointegrated corresponding to a 100% success rate. The overall mean marginal bone level change at 12 months was −0.04 ± 0.08 mm for PS group and −0.19 ± 0.16 mm for NPS group. Statistically significant difference in the marginal bone level change was observed between groups at 0 to 12 months and 3 to 12 months (P < 0.05). Conclusions This 1-year randomized control study suggests that when a conical implant–abutment connection is present, similar peri-implant tissue responses can be achieved with platform switching and non-platform switching abutments. PMID:24383912

  11. Factors associated with adherence to nucleos(t)ide analogs in chronic hepatitis B patients: results from a 1-year follow-up study.

    PubMed

    Peng, Jie; Yin, Junhua; Cai, Shaohang; Yu, Tao; Zhong, Chunxiu

    2015-01-01

    Little is known about the factors associated with patient compliance with nucleos(t)ide analog (NUC) treatment for chronic hepatitis B (CHB). The purpose of this study was to examine the association between sociodemographic and clinical characteristics and adherence to NUCs among patients with CHB. A total of 211 CHB patients receiving NUC monotherapy were asked to report the number of prescribed doses of medication they had taken during the last 90 days. A total of four 3-month adherence scores were averaged to obtain a combined rate of NUC adherence during a 1-year follow up period. The mean age of the patients was 29.6 years, 79% were men, and 68% had no prior NUC treatment for CHB. Females, patients without a previous NUC treatment, and those who had NUC drug resistance showed better adherence to NUC treatment, and compliance was better with telbivudine than with lamivudine and entecavir.

  12. Relationship between diet texture and discharge due to deteriorating health condition in nursing home residents in Japan: a multicenter 1-year prospective study.

    PubMed

    Taniguchi, Erika; Asakura, Keiko; Murakami, Kentaro; Masayasu, Shizuko; Sasaki, Satoshi

    2014-09-01

    We conducted a multicenter 1-year prospective study to evaluate the relationship between diet texture and discharge due to deteriorating health condition. The staff dietitian at each nursing home in Japan retrieved participants' data (N = 9528) from nursing records. Diet texture was categorized into 4 groups: "normal," "chopped," "pureed," and "parenteral nutrition." Discharge status was categorized into 2 groups: "discharge due to deteriorating health condition" and "stable health condition." Multivariate adjusted odds ratios and 95% confidence intervals (CIs) for "discharge due to deteriorating health condition" (n = 1820) were 1 (reference) for "normal", 1.23 (95% CI = 1.05-1.45) for "chopped," 1.82 (95% CI = 1.48-2.24) for "pureed," and 1.82 (95% CI = 1.41-2.35) for "parenteral nutrition." In conclusion, even after adjusting for baseline health status, texture-modified diets and parenteral nutrition were independently and positively associated with discharge due to deteriorating health condition.

  13. Cut off values of laser fluorescence for different storage methods at different time intervals in comparison to frozen condition: A 1 year in vitro study

    PubMed Central

    Kaul, Rudra; Kaul, Vibhuti; Farooq, Riyaz; Wazir, Nikhil Dev; Khateeb, Shafayat Ullah; Malik, Altaf H; Masoodi, Ajaz Amin

    2014-01-01

    Aims: The aim of the following study is to evaluate the change in laser fluorescence (LF) values for extracted teeth stored in different solutions over 1 year period, to give cut-off values for different storage media at different time intervals to get them at par with the in vivo conditions and to see which medium gives best results with the least change in LF values and while enhancing the validity of DIAGNOdent in research. Materials and Methods: Ninety extracted teeth selected, from a pool of frozen teeth, were divided into nine groups of 10 each. Specimens in Groups 1-8 were stored in 1% chloramine, 10% formalin, 10% buffered formalin, 0.02% thymol, 0.12% chlorhexidine, 3% sodium hypochlorite, a commercially available saliva substitute-Wet Mouth (ICPA Pharmaceuticals) and normal saline respectively at 4°C. The last group was stored under frozen condition at −20°C without contact with any storage solution. DIAGNOdent was used to measure the change the LF values at day 30, 45, 60, 160 and 365. Statistical Analysis Used: The mean change in LF values in different storage mediums at different time intervals were compared using two-way ANOVA. Results: At the end of 1 year, significant decrease in fluorescence (P < 0.05) was observed in Groups 1-8. Maximum drop in LF values occurred between day 1 and 30. Group 9 (frozen specimens) did not significantly change their fluorescence response. Conclusions: An inevitable change in LF takes place due to various storage media commonly used in dental research at different time intervals. The values obtained from our study can remove the bias caused by the storage media and the values of LF thus obtained can hence be conveniently extrapolated to the in vivo condition. PMID:24778506

  14. Emotional Development: 1 Year Olds

    MedlinePlus

    ... Español Text Size Email Print Share Emotional Development: 1 Year Olds Page Content Article Body Throughout her ... for shelter. She may seem to change from one moment to the next, or she may seem ...

  15. Social Development: 1 Year Olds

    MedlinePlus

    ... Stages Prenatal Baby Toddler Fitness Nutrition Toilet Training Preschool Gradeschool Teen Young Adult Healthy Children > Ages & Stages > Toddler > Social Development: 1 Year Olds Ages & Stages Listen Español ...

  16. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial

    PubMed Central

    McCormack, Sheena; Dunn, David T; Desai, Monica; Dolling, David I; Gafos, Mitzy; Gilson, Richard; Sullivan, Ann K; Clarke, Amanda; Reeves, Iain; Schembri, Gabriel; Mackie, Nicola; Bowman, Christine; Lacey, Charles J; Apea, Vanessa; Brady, Michael; Fox, Julie; Taylor, Stephen; Antonucci, Simone; Khoo, Saye H; Rooney, James; Nardone, Anthony; Fisher, Martin; McOwan, Alan; Phillips, Andrew N; Johnson, Anne M; Gazzard, Brian; Gill, Owen N

    2016-01-01

    Summary Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23

  17. Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.

    PubMed

    Serpell, Michael G; Notcutt, William; Collin, Christine

    2013-01-01

    Sativex is an endocannabinoid system modulator principally containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). During a 6-week randomised controlled trial, Sativex had a clinically relevant effect on spasticity associated with multiple sclerosis (MS). Patients self-titrated oromucosal Sativex to symptom relief or maximum tolerated dose (maximum of 130 mg THC and 120 mg CBD daily). The primary objective was to evaluate the safety and tolerability of long-term treatment by recording the incidence and severity of adverse events (AEs). Secondary outcomes were to determine evidence of developing tolerance and to assess the long-term dosing profile of Sativex. A validated 11-point Numerical Rating Scale of spasticity severity was used to assess efficacy. A total of 146 patients elected to enter this open-label follow-up safety trial. Mean treatment exposure was 334 days (standard deviation, SD = 209 days), and patients administered on average 7.3 (SD = 4.42) actuations per day. Fifty-two (36 %) patients withdrew from the study in the first year, 14 % due to AEs and 9 % due to lack of efficacy. Most AEs were mild/moderate in severity. Common (>10 %) treatment-related AEs were dizziness (24.7 %) and fatigue (12.3 %). Serious AEs occurred in five patients (3.4 %), with two psychiatric events reported by one patient. No psychoses, psychiatric AE trends, or withdrawal symptoms occurred following abrupt cessation of treatment. Baseline symptoms including spasticity did not deteriorate but were maintained to study completion in those patients who did not withdraw. No new safety concerns were identified with chronic Sativex treatment, and serious AEs were uncommon. There was no evidence of tolerance developing, and patients who remained in the study reported continued benefit. PMID:22878432

  18. Influence of Two Colloidal Extracorporeal Primes on Coagulation of Cardiac Surgical Patients: A Prospectively Randomized Open-Label Pilot Trial.

    PubMed

    Bethlehem, Irene; Wierda, Korry; Visser, Cornelis; Jekel, Lilian; Koopmans, Matty; Kuiper, Michael A

    2014-12-01

    The search for the ideal priming fluid continues as more evidence is discovered about side effects of volume expanders. With the availability of modern, balanced hydroxyethyl starch (HES) solutions with less side effects than former HES solutions, we considered to replace our gelatin- (modified gelatin) based extracorporeal circuit prime for a HES (130/.42) prime. Therefore, we studied the influence of two colloidal priming fluids on postoperative coagulation in patients undergoing cardiac surgery. The primary endpoint was to compare clot formation time between the HES group and the gelatin group with rotational thromboelastometry (ROTEM). Additionally we compared colloid osmotic pressure and fluid balance of both groups. Forty patients, undergoing elective first time coronary artery bypass grafting or single-valve surgery, were included in this prospectively randomized open-label pilot study. Laboratory data and ROTEM data were collected and analyzed for differences between the two groups. ROTEM data show significantly more prolongation in Extem clot formation time and significant more decrease in Extem alpha in the HES group. Fibtem maximum clot firmness was significantly smaller in the HES group; this was consistent with fibrinogen concentration measurement, which decreased more in the HES group than in the gelatin group and recovered more over time in the gelatin group. We found no significant difference in colloid. osmotic pressure between the groups. In this trial, HES (130/.42) impairs coagulation significantly more compared with gelatin. These differences in influence on coagulation did not lead to a difference in blood loss or fluid balance, so clinical relevance could not be proven. PMID:26357798

  19. Neural correlates of change in major depressive disorder anhedonia following open-label ketamine.

    PubMed

    Lally, Níall; Nugent, Allison C; Luckenbaugh, David A; Niciu, Mark J; Roiser, Jonathan P; Zarate, Carlos A

    2015-05-01

    Anhedonia is a cardinal symptom of major depression and is often refractory to standard treatment, yet no approved medication for this specific symptom exists. In this exploratory re-analysis, we assessed whether administration of rapid-acting antidepressant ketamine was associated specifically with reduced anhedonia in medication-free treatment-refractory patients with major depressive disorder in an open-label investigation. Additionally, participants received either oral riluzole or placebo daily beginning 4 hours post-infusion. A subgroup of patients underwent fluorodeoxyglucose positron emission tomography scans at baseline (1-3 days pre-infusion) and 2 hours post-ketamine infusion. Anhedonia rapidly decreased following a single ketamine infusion; this was sustained for up to three days, but was not altered by riluzole. Reduced anhedonia correlated with increased glucose metabolism in the hippocampus and dorsal anterior cingulate cortex (dACC) and decreased metabolism in the inferior frontal gyrus and orbitofrontal cortex (OFC). The tentative relationship between change in anhedonia and glucose metabolism remained significant in dACC and OFC, and at trend level in the hippocampus, a result not anticipated, when controlling for change in total depression score. Results, however, remain tenuous due to the lack of a placebo control for ketamine. In addition to alleviating overall depressive symptoms, ketamine could possess anti-anhedonic potential in major depressive disorder, which speculatively, may be mediated by alterations in metabolic activity in the hippocampus, dACC and OFC.

  20. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial

    PubMed Central

    Dondorp, Arjen M; Fanello, Caterina I; Hendriksen, Ilse CE; Gomes, Ermelinda; Seni, Amir; Chhaganlal, Kajal D; Bojang, Kalifa; Olaosebikan, Rasaq; Anunobi, Nkechinyere; Maitland, Kathryn; Kivaya, Esther; Agbenyega, Tsiri; Nguah, Samuel Blay; Evans, Jennifer; Gesase, Samwel; Kahabuka, Catherine; Mtove, George; Nadjm, Behzad; Deen, Jacqueline; Mwanga-Amumpaire, Juliet; Nansumba, Margaret; Karema, Corine; Umulisa, Noella; Uwimana, Aline; Mokuolu, Olugbenga A; Adedoyin, Olanrewaju T; Johnson, Wahab BR; Tshefu, Antoinette K; Onyamboko, Marie A; Sakulthaew, Tharisara; Ngum, Wirichada Pan; Silamut, Kamolrat; Stepniewska, Kasia; Woodrow, Charles J; Bethell, Delia; Wills, Bridget; Oneko, Martina; Peto, Tim E; von Seidlein, Lorenz; Day, Nicholas PJ; White, Nicholas J

    2010-01-01

    Summary Background Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria. Methods This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054. Findings 5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63–0·90; relative reduction 22·5%, 95% CI 8·1–36·9; p=0·0022). Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49–0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66–0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64–0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients. Post

  1. An Open Label Comparison of Calfactant and Poractant Alfa Administration Traits and Impact on Neonatal Intensive Care Unit Resources

    PubMed Central

    Gerdes, Jeffrey S.; Seiberlich, William; Sivieri, Emidio M.; Marsh, Wallace; Varner, Dwight L.; Turck, Charles J; York, John M.

    2006-01-01

    OBJECTIVE To compare calfactant (CA) and poractant alfa (PA) administration traits, short-term clinical responses, and resource use in the neonatal respiratory distress syndrome (RDS) setting. METHODS An open label series of 277 (213 PA and 64 CA) infants was evaluated for 445 administrations. Registered respiratory therapists collected patient, surfactant administration, and postadministration clinical data. Economic analysis involved labor costs of surfactant administration and usage, wastage, and product average wholesale price. Analysis utilized the Mann-Whitney rank sum test for differences in administration time and either the chi-square or Fisher's exact test for categorical variables. RESULTS PA had a statistically lower bedside administration time than CA (3.8 minutes vs. 5.3 minutes; P = .006) and a higher percentage of doses administered in less than five minutes (58.9% vs. 4.3%; P < .001). Doses administered per patient were similar (1.67 vs. 1.72). PA and CA were similar in time to recovery (81.4% vs. 74.3%), percent desaturation (24.8% vs. 26.7%), and bradycardia (3.8% vs. 8.5%). Reflux was significantly higher (13.2% vs. 3.5%; P < .001) with CA. Economic analyses found total administration costs per dose were $2.21 for PA and $3.08 for CA. Mean wastage costs were $141.21 for PA and $337.34 for CA (P < .001). CONCLUSIONS PA appeared to utilize fewer neonatal intensive care unit resources than CA due to reduced administration time and less wastage of drug product. Future studies should more closely evaluate time, resource, wastage, and post-administrative clinical effects to fully assess the impact of surfactant products in this setting. PMID:23118647

  2. Sevoflurane versus propofol sedation during periocular anesthetic injections in oculoplastic procedures: An open-label randomized comparison

    PubMed Central

    Tawfik, Hatem A.; Mostafa, Mohsen

    2014-01-01

    Purpose The purpose of the current investigation was to make an objective controlled comparison of pain tolerance, patient satisfaction and potential complications during the injection of local anesthesia in oculoplastic procedures under short-term sedation using inhalational versus parenteral sedatives. Methods This was an open-label, randomized clinical trial where patients were randomized to 3 groups. Group I: Sedation with intravenous propofol. Group II: Sedation with inhaled sevoflurane. Group 3: Control group receiving no sedation. Results A total of 396 patients were randomly assigned, and 375 were included in the final analysis. Study groups were similar in age, gender, and distribution of operative procedures performed. There was no statistically significant difference in the adjusted primary composite outcome measure between propofol and sevoflurane (pain scores and patient satisfaction). Significantly more patients in group I required restraining during periocular injections than group II or III (p < 0.001). Significantly more patients sneezed in group I than group II (p < 0.001) and none in the control group. Three patients in group II suffered severe excitation–disinhibition during emergence from sedation which was rapidly reversible, and 3 more suffered a severe bout of postoperative nausea and vomiting (PONV). Conclusion Sevoflurane and propofol during periocular anesthetic injections produce an equally favorable experience. Sevoflurane is introduced painlessly, and offers better patient control with less induction of the sneezing reflex which may provide a higher safety profile, however short-term aggression/disinhibition and PONV may be an issue in some patients. PMID:25892931

  3. Initial combination of linagliptin and metformin in patients with type 2 diabetes: efficacy and safety in a randomised, double-blind 1-year extension study

    PubMed Central

    Haak, T; Meinicke, T; Jones, R; Weber, S; von Eynatten, M; Woerle, H-J

    2013-01-01

    Objective To determine the efficacy and safety of linagliptin in initial combination with metformin in patients with type 2 diabetes. Methods This 1-year randomised, double-blind study was an extension of a 6-month randomised controlled trial, in which adults with type 2 diabetes received one of six treatment regimens (linagliptin 2.5 mg plus metformin 500 mg bid, linagliptin 2.5 mg plus metformin mg 1000 bid, metformin 1000 mg bid, metformin 500 mg bid, linagliptin 5 mg qd or placebo). In the extension, patients in the first three treatment groups continued their regimen (non-switched group, n = 333) while the metformin 500 mg bid, linagliptin 5 mg qd and placebo groups were re-randomised to one of the three continuing regimens (switched group, n = 233). Results All three non-switched groups maintained reductions in glycosylated haemoglobin (HbA1c; mean ± standard deviation reductions across the 1.5-year period: linagliptin 2.5 plus metformin 1000 bid, –1.63 ± 1.05%; linagliptin 2.5 plus metformin 500 bid, –1.32 ± 1.06%; metformin 1000 bid, –1.25 ± 0.91%) while the switched groups showed additional HbA1c reductions. During the extension, there were no clinically meaningful changes in body weight in any group. Adverse event rates were similar between groups, with most events being mild or moderate, and the incidence of investigator-defined hypoglycaemia was low, with no severe events. Discussion Initial combination of linagliptin and metformin was well tolerated over the 1-year extension period, with low risk of hypoglycaemia, and improved glycaemic control vs. metformin alone. Conclusion The initial combination of linagliptin and metformin appears to provide a useful treatment option in patients whose blood glucose levels are increased to an extent that metformin monotherapy may not achieve treatment targets. PMID:24118640

  4. Outcome of venous stenting following catheter directed thrombolysis for acute proximal lower limb venous thrombosis: a prospective study with venous Doppler follow-up at 1-year.

    PubMed

    Srinivas, B C; Patra, Soumya; Reddy, Babu; Nagesh, C M; Agarwal, Naveen; Manjunath, C N

    2015-10-01

    Functional outcome of venous stent placement for the management of acute iliofemoral deep vein thrombosis (DVT) following catheter-directed thrombolysis (CDT), remain undefined. The purpose of this study was to assess immediate and intermediate term outcomes among patients treated with venous stenting following CDT in patients with proximal lower limb DVT. Thirty consecutive patients aged between 20-70 years with proximal lower limb DVT formed the study group. The mean duration of CDT done with streptokinase was 4.5 ± 1.3 days. Patients with residual venous obstruction and/or large clot burden were treated further with venous angioplasty and/or stenting. Primary endpoint was to evaluate the safety, efficacy and patency of venous stenting in the management of incomplete result following CDT. After 12 months, post-thrombotic syndrome (PTS) was assessed clinically using Villalta scale and deep venous patency was assessed through duplex ultrasound. We studied 8 (5 female and 3 male) patients with 9 (3 left and 6 right) limb involvement and 13 stent (4 balloon expandable and 9 self expandable) placement. All patients improved clinically immediately following venous stenting. Technical success was achieved in all patients. One patient developed pulmonary embolism during course of hospital stay. One patient had stent thrombosis and PTS and another patient died due to carcinoma breast during follow-up. Deep venous stenting is an effective mode of treatment in proximal acute lower limb DVT with high late patency rate up to 1-year.

  5. Outcomes of West Nile encephalitis patients after 1 year of West Nile encephalitis outbreak in Kerala, India: A follow-up study.

    PubMed

    Balakrishnan, Anukumar; Thekkekara, Romy Jose; Tandale, Babasheb V

    2016-11-01

    We reported an acute encephalitis syndrome outbreak in Alappuzha district in Kerala, India during the year 2011. The etiology was confirmed to be West Nile virus lineage 1. Many encephalitis patients from this outbreak exhibited neurological sequelae post recovery. This study was aimed to assess the clinical outcomes of West Nile encephalitis confirmed case-patients after 1 year of acute illness. Forty West Nile virus confirmed encephalitis patients were selected from the 2011 outbreak was included in this study. Out of 40 cases, only 30 survived after 12 months. Among these 30 recovered case-patients, 27 (90%) consented for clinical follow-up and 23 (73.67%) of them consented for assessment of cognitive impairment and deposition of blood sample for antibody testing. The most common symptom observed in these patients was fatigue (25.93%). Other symptoms included dizziness (7.4%), decreased sense of hearing (7.4%) and decreased sense of smell (7.4%). Reduced power in limbs was found in 33.33% of the cases. Most of the patients (23.1%) were dependent on others for normal daily living activities. The patients also had probable risk of poor cognition (29.41%) and dementia (57.14%). None of the patients were positive for WNV specific IgM at 12 months post onset of disease. The study concluded that the long-term sequelae were noticed in WNV positive patients. Prevention effort should be focused on the elderly (≥60 years old) people who have a higher risk of severe sequelae. The state health authorities should create awareness among people in order to prevent the transmission of disease. J. Med. Virol. 88:1856-1861, 2016. © 2016 Wiley Periodicals, Inc. PMID:27061922

  6. Outcomes of West Nile encephalitis patients after 1 year of West Nile encephalitis outbreak in Kerala, India: A follow-up study.

    PubMed

    Balakrishnan, Anukumar; Thekkekara, Romy Jose; Tandale, Babasheb V

    2016-11-01

    We reported an acute encephalitis syndrome outbreak in Alappuzha district in Kerala, India during the year 2011. The etiology was confirmed to be West Nile virus lineage 1. Many encephalitis patients from this outbreak exhibited neurological sequelae post recovery. This study was aimed to assess the clinical outcomes of West Nile encephalitis confirmed case-patients after 1 year of acute illness. Forty West Nile virus confirmed encephalitis patients were selected from the 2011 outbreak was included in this study. Out of 40 cases, only 30 survived after 12 months. Among these 30 recovered case-patients, 27 (90%) consented for clinical follow-up and 23 (73.67%) of them consented for assessment of cognitive impairment and deposition of blood sample for antibody testing. The most common symptom observed in these patients was fatigue (25.93%). Other symptoms included dizziness (7.4%), decreased sense of hearing (7.4%) and decreased sense of smell (7.4%). Reduced power in limbs was found in 33.33% of the cases. Most of the patients (23.1%) were dependent on others for normal daily living activities. The patients also had probable risk of poor cognition (29.41%) and dementia (57.14%). None of the patients were positive for WNV specific IgM at 12 months post onset of disease. The study concluded that the long-term sequelae were noticed in WNV positive patients. Prevention effort should be focused on the elderly (≥60 years old) people who have a higher risk of severe sequelae. The state health authorities should create awareness among people in order to prevent the transmission of disease. J. Med. Virol. 88:1856-1861, 2016. © 2016 Wiley Periodicals, Inc.

  7. Artesunate–mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial

    PubMed Central

    Grigg, Matthew J; William, Timothy; Menon, Jayaram; Dhanaraj, Prabakaran; Barber, Bridget E; Wilkes, Christopher S; von Seidlein, Lorenz; Rajahram, Giri S; Pasay, Cielo; McCarthy, James S; Price, Ric N

    2016-01-01

    Summary Background The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate–mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children. Methods We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate–mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01708876. Findings Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate–mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76–91]) of 115 patients in the artesunate–mefloquine group versus 61 (55% [45–64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0–40·8]; p<0·0001). Parasite clearance was faster in patients given artesunate–mefloquine than in those given chloroquine (18·0 h [range 6·0–48·0] vs 24·0 h [6·0–60·0]; p<0·0001), with faster clearance of ring stages in the artesunate–mefloquine group (mean time to 50% clearance

  8. Tazemetostat Rollover Study (TRuST): An Open-Label Rollover Study

    ClinicalTrials.gov

    2016-09-13

    Diffuse Large B-cell Lymphoma; Follicular Lymphoma; Malignant Rhabdoid Tumors (MRT); Rhabdoid Tumors of the Kidney (RTK); Atypical Teratoid Rhabdoid Tumors (ATRT); Synovial Sarcoma; Epitheliod Sarcoma; Mesothelioma; Advanced Solid Tumors

  9. Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized, Double-Blind, Placebo-Controlled Trial with Open-Label Extension

    PubMed Central

    Koh, Jung-Min; Chung, Dong Jin; Chung, Yoon-Sok; Kang, Moo-Il; Kim, In-Ju; Min, Yong-Ki; Oh, Han-Jin; Park, Il Hyung; Lee, Yil-Seob; Waterhouse, Brian; Nino, Antonio; Fitzpatrick, Lorraine A.

    2016-01-01

    Purpose The efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study. Materials and Methods Women aged 60 to 90 years with a T-score of <-2.5 and ≥-4.0 at the lumbar spine or total hip were randomized to a single 60 mg subcutaneous dose of denosumab or placebo for the 6-month double-blind phase. Eligible subjects entered the 6-month open-label extension phase and received a single dose of denosumab 60 mg. Results Baseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals. Conclusion Denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women. PMID:27189284

  10. Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease: A 1-Year, Multicenter, Randomized, Placebo-Controlled Study

    PubMed Central

    Karpecki, Paul M.; Majmudar, Parag A.; Nichols, Kelly K.; Raychaudhuri, Aparna; Roy, Monica; Semba, Charles P.

    2016-01-01

    Purpose: To evaluate the 1-year safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease compared with placebo. Methods: SONATA (Safety Of a 5.0% coNcentrATion of lifitegrAst ophthalmic solution) was a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 study (NCT01636206). Adults (≥18 years) with dry eye disease (Schirmer test score ≥1 and ≤10 mm; corneal staining score ≥2.0) were randomized 2:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 360 days. The primary objective was percentage and severity of treatment-emergent adverse events (TEAEs). Secondary objectives were ocular safety measures: corneal fluorescein staining, drop comfort, best-corrected visual acuity, slit-lamp biomicroscopy, and intraocular pressure over 7 visits. Exploratory objectives included concentration of lifitegrast in plasma. Results: The safety population comprised 331 participants (220 lifitegrast; 111 placebo). There were no serious ocular TEAEs. Overall, 53.6% of participants receiving lifitegrast experienced ≥1 ocular TEAE versus 34.2% in the placebo group; most TEAEs were mild to moderate in severity. Rates of discontinuation because of TEAEs were 12.3% (lifitegrast) versus 9.0% (placebo). The most common (>5%) TEAEs occurring in either treatment group were instillation site irritation (burning), instillation site reaction, visual acuity reduced, dry eye, and dysgeusia (change in taste). Ocular safety parameters for lifitegrast were similar to placebo. The mean plasma lifitegrast concentration at 360 days (n = 43) was below the limit of detection. There was no indication of systemic toxicity or localized infectious complications secondary to chronic immunosuppression. Conclusions: Lifitegrast ophthalmic solution 5.0% seemed safe and well tolerated in this study, with no unexpected adverse events. PMID:27055211

  11. Patterns of Non-adherence to Supplementation with Calcium and Vitamin D in Persistent Postmenopausal Women Are Similar at Start and 1 Year Later: A Qualitative Longitudinal Study

    PubMed Central

    Touskova, Tereza; Vytrisalova, Magda; Palicka, Vladimir; Hendrychova, Tereza; Chen, Yang-Ti; Fuksa, Leos

    2016-01-01

    Background: Osteoporosis is a chronic disease and adherence can fluctuate over time. Therefore, longer observation is necessary to investigate the stability of patients' adherence. The study aim was to compare the overall adherence (OA) to supplementation with the fixed combination of calcium and vitamin D (Ca/D) in postmenopausal women at baseline and after 1 year, and to evaluate the fluctuation of the OA in individual months. Furthermore, we studied whether adherence is influenced by signing of informed consent and routine medical check-up. Methods: This was a longitudinal, observational study. The data were obtained from the Osteocenter of University Hospital in Hradec Kralove, Czech Republic. Adherence was measured using electronic bottles type Medication Events Monitoring System (MEMS). The study was carried out in two 3-month periods; the baseline in 2013 (signing of informed consent while medical check-up) and the follow-up (medical check-up) in 2014. The adherence and adherence-related outcomes were studied in patients who had initiated osteoporosis treatment and were persistent. Results: 21 (49%) out of 43 patients who avoided drug dispenser and were persistent both at baseline and at follow-up, completed the study and were included. Median age was 76. Evaluating the whole 3-month periods, the OA did not differ significantly at baseline and at follow-up, the OA was 71 and 68%, respectively. However, the adherence in month 1 at baseline was significantly higher than the adherence in month 2 at baseline (p < 0.001) and also than the adherence in month 1 at follow-up (p = 0.010). Analysing the study period without month 1, a stable adherence was observed in 48% of patients. About 33% of doses were omitted at baseline and 34% at follow-up. As many as 71% of the patients took drug holidays at baseline, and 76% at follow-up. Conclusion: The OA was insufficient, around 70% both at baseline and at follow-up. One half of the patients showed a stable adherence. The

  12. The influence of soft tissue biotype on the marginal bone changes around dental implants: A 1-year prospective clinico-radiological study

    PubMed Central

    Bhat, Pragathi Raghavendra; Thakur, Srinath Lakshman; Kulkarni, Sudhindra Sushilendra

    2015-01-01

    Background: The peri-implant mucosa undergoes surgical and bacterial assaults in various stages of implant therapy, however, the literature on changes occurring in the peri-implant mucosa is minimal. This study was thus conducted to evaluate the change in the peri-implant mucosal thickness and its effect on the marginal bone levels around dental implants treated in a conventional two-stage implant therapy. Materials and Methods: A total of 36 implants were placed in 22 subjects. Two subjects dropped out. Thirty-three implants in 20 subjects were then evaluated. Initial mucosal thickness, marginal bone levels on radiographs, pain, and exudation were evaluated. All these parameters were recorded at the time of implant placement, at the time of cementation of final restoration, 6 months and 12 months post cementation/restoration. Results: The peri-implant mucosal thickness reduced from implant placement to second stage and till restorations and was statistically significant, in both the thick and thin biotypes, however, at 12 months there was a rebound of the tissue thickness, which was more in the thick biotype (P < 0.05). At 1-year follow-up, there was a reduction in the marginal bone levels, which was more in the thick biotype as compared to the thin biotype (P < 0.05). Conclusion: The mucosa at implant sites undergoes a reduction in thickness from the time of implant placement till the placement of final restorations. The placement of the final restorations and then end of active therapy leads to a rebound of the tissue thickness. Sites with thicker tissues preoperatively have a lesser bone loss and better rebound as compared to thinner tissues. PMID:26941514

  13. Impact of maternal prenatal and parental postnatal stress on 1-year-old child development: results from the OTIS antidepressants in pregnancy study.

    PubMed

    Karam, Fatiha; Sheehy, Odile; Huneau, Marie-Claude; Chambers, Christina; Fraser, William D; Johnson, Diana; Kao, Kelly; Martin, Brigitte; Riordan, Sara H; Roth, Mark; St-André, Martin; Lavigne, Sharon Voyer; Wolfe, Lori; Bérard, Anick

    2016-10-01

    Perinatal psychological stress has been associated with unfavorable maternal and neonatal outcomes. We aimed to assess the impact of perinatal stress on infant development at 1 year of age. We recruited pregnant women calling North American Teratogen Information Services or attending outpatient clinics at CHU Sainte Justine (Montreal) between 2008 and 2010 and their spouses. To be part of our study, women had to be (1) >18 years of age, (2) <15 weeks of gestational age at recruitment, (3) living within 250-km radius of Montreal, and (4) taking antidepressants or non-teratogenic drugs. Stress was assessed using the telephone-administered four-item perceived stress scale during pregnancy in mothers and at 2 months postpartum in both parents. Child development at 1 year of age was evaluated with the Bayley III scales. Socio-demographic and potential confounders were collected through telephone interviews. Multivariable linear regression models were built to assess the association between perinatal parental stress and child development. Overall, 71 couples and their infants were included. When adjusted for potential confounders, maternal prenatal stress was positively associated with motor development (adjusted β = 1.85, CI 95 % (0.01, 3.70)). Postpartum maternal and paternal stresses were negatively associated with motor and socio-emotional development, respectively (adjusted β = -1.54, CI 95 % (-3.07, -0.01) and adjusted β = -1.67, CI 95 % (-3.25, -0.10), respectively). Maternal and paternal postnatal stress seems to be harmful for the motor and socio-emotional development in 1-year-old children. No association was demonstrated between parental stress and cognitive, language, and adaptive behavioral development. However, prenatal maternal stress appears to improve motor skills. PMID:26957509

  14. A Comparison of Acellular Dermal Matrix Allograft and Periosteal Pedicle Graft Covered by Coronally Advanced Flap in the Treatment of Gingival Recession: 1-Year Follow-Up Study.

    PubMed

    Godavarthi, Lalasa; Murthy, K Raja; Pavankumar, Sandhya

    2016-01-01

    The objective of this study was to evaluate and compare the clinical efficacy of periosteal pedicle graft (PPG) and acellular dermal matrix allograft (ADMA) in conjunction with coronally advanced flap (CAF) in the treatment of gingival recession during a 1-year follow-up. A sample of 14 patients, each with two similar Miller Class I or II gingival recession (28 recession sites), was selected. Each recession site was randomly assigned to the experimental site (PPG + CAF) or the control site (ADMG + CAF). The clinical parameters recorded at baseline and 12 months postoperatively were probing pocket depth, width of keratinized gingiva, and clinical attachment level, whereas full-mouth and site-specific plaque and gingival index and vertical recession depth and width were recorded at baseline and at 1, 3, 6, 9, and 12 months. Analysis was performed to determine if treatment differences were present. The mean recession depth in experimental sites decreased from 2.89 ± 0.40 mm at baseline to 0.25 ± 0.50 mm at 12 months, corresponding to a mean root coverage of 92.79% ± 14.25%. In control sites, recession shrank from 2.93 ± 0.55 mm at baseline to 0.32 ± 0.46 mm at 12 months follow-up, demonstrating a mean root coverage of 89.79% ± 14.73%. Compared to the use of ADMA, the PPG technique uses similar incision design and flap management at the graft site, is equivalent in technique sensitivity, and has a perceived improvement in esthetic outcome. PMID:27333020

  15. Development of Interests and Competency Beliefs: A 1-Year Longitudinal Study of Fifth- to Eighth-Grade Students Using the ICA-R and Structural Equation Modeling

    ERIC Educational Resources Information Center

    Tracey, Terence J. G.

    2002-01-01

    The relative influence of interest and self-efficacy beliefs on each other over 1 year was examined in 2 longitudinal samples of students, 1 of elementary school students (Grade 5, N = 126) and 1 of middle school students (Grade 7, N = 221). Interest and competence ratings on the Realistic, Investigative, Artistic, Social, Enterprising, and…

  16. Dynamics of resilience in forced migration: a 1-year follow-up study of longitudinal associations with mental health in a conflict-affected, ethnic Muslim population

    PubMed Central

    Siriwardhana, Chesmal; Abas, Melanie; Siribaddana, Sisira; Sumathipala, Athula; Stewart, Robert

    2015-01-01

    Objective The concept of ‘resilience’ is of increasing interest in studies of mental health in populations facing adversity. However, lack of longitudinal data on the dynamics of resilience and non-usage of resilience-specific measurements have prevented a better understanding of resilience-mental health interactions. Hence, the present study was conducted to investigate the stability of levels of resilience and its associations with sociodemographic and mental health exposures in a conflict-affected internal-migrant population in Sri Lanka. Design A prospective follow-up study of 1 year. Setting Puttalam district of North Western province in postconflict Sri Lanka (baseline in 2011, follow-up in 2012). Participants An ethnic Muslim population internally displaced 20 years ago (in 1990) from Northern Sri Lanka, aged 18 or above and currently in the process of return migration. Measures It was hypothesised that levels of resilience would be associated with mental health outcomes. Resilience was measured on both occasions using the 14-item Resilience Scale (RS-14), social support by the Multidimensional Social Support Scale and Lubben Social Network Scale and common mental disorders by the Patient Health Questionnaire (PHQ). Results Of 450 participants interviewed at baseline in 2011, 338 (75.1%) were re-interviewed in 2012 after a 1-year follow-up. The mean resilience scores measured by RS-14 were 80.2 (95% CI 78.6 to 81.9) at baseline and 84.9 (83.5 to 86.3) at follow-up. At both time points, lower resilience was independently associated with food insecurity, lower social support availability and social isolation. At both time points, there were significant associations with common mental disorders (CMDs) in unadjusted analyses, but they only showed independence at baseline. The CMD prevalence, maintenance and incidence at follow-up was 8.3%, 28.2% and 2.2%, respectively. Conclusions In this displaced population facing a potential reduction in adversity

  17. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial

    PubMed Central

    Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John MS; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

    2009-01-01

    Summary Background Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. Methods In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2 at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m2 at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m2 at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. Findings All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0·95, 95% CI 0·85–1·08; p=0·44). 75·6% (95% CI 73·7–77·5) of patients in the experimental group and 74·3% (72·3–76·2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0·0001); the most frequent events were neutropenia (937 events vs 797 events

  18. Montelukast in the treatment of perennial allergic rhinitis in paediatric Japanese patients; an open-label clinical trial

    PubMed Central

    Okubo, Kimihiro; Inoue, Yoichi; Numaguchi, Hirotaka; Tanaka, Kumi; Saito, Itori; Oshima, Nobuyuki; Matsumoto, Yuki; Prohn, Marita; Mehta, Anish; Nishida, Chisato; Philip, George

    2016-01-01

    Abstract Background: This study was conducted to evaluate the safety and tolerability, and population pharmacokinetics (PPK) of montelukast as well as efficacy in the treatment of perennial allergic rhinitis (PAR) in paediatric Japanese patients aged between 1 and 15 years. Methods: In this multi-centre, open-label trial, 87 paediatric Japanese patients with PAR received montelukast 4 mg oral granules (OG) for 4 weeks (1–5-year-olds, N = 15), 4 mg OG for 12 weeks (1–5-year-olds, N = 36), 5 mg chewable tablets (CT) for 12 weeks (6–9-yea